Kallikrein 7 modulators

ABSTRACT

The present invention relates to the crystal structure of the serine protease kallikrein 7 and to the use of this crystal structure in drug discovery. The present invention also relates to compounds binding specifically to this active site of kallikrein 7.

FIELD OF THE INVENTION

The present invention relates to the crystal structure of the serineprotease kallikrein 7 and to the use of this crystal structure in drugdiscovery. The present invention also relates to compounds bindingspecifically to this active site of kallikrein 7.

BACKGROUND OF THE INVENTION

Kallikrein 7 is a S1 serine protease of the kallikrein gene familydisplaying a chymotrypsin like activity. Human kallikrein 7 (hK7, KLK7or stratum corneum chymotryptic enzyme (SCCE), Swissprot P49862) ismainly expressed in the skin and appears to play an important role inskin physiology (1, 2, 3). hK7 is involved in the degradation of theintercellular cohesive structure in cornified squamous epithelia in theprocess of desquamation. The desquamation process is well regulated anddelicately balanced with the de novo production of corneocytes tomaintain a constant thickness of the stratum corneum. In this regard,hK7 is reported to be able to cleave the corneodesmosomal proteinscorneodesmosin and desmocollin 1 (4, 5, 6). In addition, recently it hasbeen shown that the two lipid processing enzymes β-glucocerebrosidaseand acidic sphingomyelinase can be degraded by hK7 (7). Both lipidprocessing enzymes are co-secreted with their substratesglucosylceramides and sphingomyelin and process these polar lipidprecursors into their more non-polar products e.g. ceramides, which aresubsequently incorporated into the extracellular lamellar membranes. Thelamellar membrane architecture is critical for a functional skinbarrier. Finally, hK7 has been shown to activate the pro-inflammatorycytokine Pro-interleukin-1β (IL-1β) (8) and to (in)activatecathelicidines (hCAP18) which regulate an important defense mechanism toprevent infections against a wide variety of microbial pathogens (34).

Recent studies link an increased activity of hK7 to inflammatory skindiseases like atopic dermatitis, psoriasis or Netherton's syndrome. Anincreased hK7 activity might lead to an uncontrolled degradation ofcorneodesmosomes resulting in a miss-regulated desquamation, an enhanceddegradation of lipid processing enzymes resulting in a disturbedlamellar membrane architecture or an uncontrolled (in)activation of thepro-inflammatory cytokine IL-1β or the cathilicidin hCAP18. The netresult could lead to an impaired skin barrier function and inflammation(see also WO-A-2004/108139).

The hK7 activity is controlled on several levels. Various factors mightbe responsible for an increased hK7 activity in inflammatory skindiseases. Firstly, the amount of protease being expressed might beinfluenced by genetic factors. Such a genetic link, a polymorphism inthe 3′-UTR in the hK7 gene, was recently described (9). The authorshypothesis that the described 4 base pair insertion in the 3′-UTR of thekallikrein 7 gene stabilizes the hK7 mRNA and results in anoverexpression of hK7. Secondly, since hK7 is secreted via lamellarbodies to the stratum corneum extracellular space as zymogen and it isnot able to autoactivate, it needs to be activated by another proteasee.g. kallikrein 5 (5). Uncontrolled activity of such an activatingenzyme might result in an overactivation of hK7. Thirdly, activated hK7can be inhibited by natural inhibitors like LEKTI, ALP or elafin (10,11). The decreased expression or the lack of such inhibitors mightresult in an enhanced activity of hK7. Recently it was found, thatmutations in the spink5 gene, coding for LEKTI, are causative forNetherton's syndrome (12) and a single point mutation in the gene islinked to atopic dermatitis (13, 14). Finally, another level ofcontrolling the activity of hK7 is the pH. hK7 has a neutral to slightlyalkaline pH optimum (2) and there is a pH gradient from neutral toacidic from the innermost to the outermost layers in the skin.Environmental factors like soap might result in a pH increase in theoutermost layers of the stratum corneum towards the pH optimum of hK7thereby increasing the hK7 activity.

The hypothesis that an increased activity of hK7 is linked toinflammatory skin diseases is supported by the following studies:Firstly, Netherton's syndrome patients show a phenotype dependentincrease in serine protease activity, a decrease in corneodesmosomes, adecrease in the lipid processing enzymes (3-glucocerebrosidase andacidic sphingomyelinase, and an impaired barrier function (15, 16).Secondly, a transgenic mice overexpressing human kallikrein 7 shows askin phenotype similar to that found in patients with atopic dermatitis(17, 18, 19). Thirdly, in the skin of atopic dermatitis and psoriasispatients elevated levels of hK7 were described (17, 20).

Therefore, hK7 is considered to be a potential target for the treatmentof inflammatory skin diseases like atopic dermatitis, psoriasis orNetherton's syndrome and there is a need for specific modulators(agonists or inhibitors) thereof.

In order to fulfill this need, the present inventors have developedmethods for cloning, expression, purification and crystallization ofhK7, and have been able to obtain for the first time the structure ofhuman kallikrein 7 at a very high resolution.

This structure of human kallikrein 7 at a very high resolution hasallowed for the identification of the active site of the enzyme, andcompounds binding specifically to said active site of kallikrein 7.

SUMMARY OF THE INVENTION

In order to fulfill the needs identified herein-above, the presentinventors have developed methods for cloning, expression, purificationand crystallization of hK7, and have been able to obtain for the firsttime the structure of human kallikrein 7 at a very high resolution. Theobtained structure of human kallikrein 7 at a very high resolution hasallowed to identify the active site of the enzyme and compounds bindingspecifically to said active site of kallikrein 7. The present inventorshave furthermore been able to confirm that these compounds have amodulatory effect on kallikrein 7.

The present invention thus pertains to a crystal of human kallikrein 7comprising the binding pocket having a three-dimensional structurecharacterized by the structure coordinates of Table 3 below. Thiscrystal can also comprise a co-crystallised ligand.

The present invention also pertains to a computer readable mediumcomprising data storage material encoded with computer readable datawherein said data comprises the structure coordinates of a crystalaccording to the invention, and to the use of this crystal for thegeneration of crystal structure data.

Another embodiment of the present invention is a method of identifying aligand that binds to kallikrein 7, this method comprising the steps of(i) using the three dimensional structure data generated according tothe invention to select and/or design a potential ligand that binds tokallikrein 7, and (ii) identifying among the potential ligand selectedin step (i), those ligands that bind to kallikrein 7 in an in vitro, invivo or cell-based assay.

Yet another embodiment of the present invention relates to a modulatorof kallikrein 7 characterised in that it binds in the binding pockethaving a three-dimensional structure characterized by the structurecoordinates of Table 3. This modulator of kallikrein 7 can be a compoundof formula

wherein

-   -   R₁ is hydrogen, cyano, (C₁₋₈)alkyl, (C₂₋₈)alkenyl,        (C₂₋₈)alkynyl, halogen, (C₁₋₈)alkylamino,        (C₁₋₈)alkylamino(C₁₋₈)alkyl, (C₁₋₈)alkoxy, halo(C₁₋₈)alkyl,    -   X is CH═CH, NH, N═CH, O or S,    -   Y is a group of formula

-   -   wherein        -   the N-containing ring system is optionally annelated with            (C₃₋₈)cycloalkyl, (C₈₋₁₈)aryl or heterocyclyl having 5 to 6            ring members and 1 to 4 heteroatoms selected from N, O, S,        -   n is 1, 2 or 3,        -   R₂ is            -   (C₁₋₈)alkyl, (C₁₋₈)alkylamino,                (C₁₋₈)alkylamino(C₁₋₈)alkyl,                di(C₁₋₈)alkylamino(C₁₋₈)alkyl, halo(C₁₋₈)alkyl,                (C₁₋₈)alkoxy, (C₁₋₈)alkoxy(C₁₋₈)alkyl, or            -   (CH₂)_(m)-Z, wherein Z is unsubstituted or substituted                (C₃₋₈)cycloalkyl, (C₆₋₁₈)aryl or heterocyclyl having 5                to 6 ring members and 1 to 4 heteroatoms selected from                N, O, S and m is 0, 1 or 2,        -   R₃ is hydrogen, (C₁₋₈)alkyl, (C₁₋₈)alkoxy, (C₆₋₁₈)aryl or            heterocyclyl having 5 to 6 ring members and 1 to 4            heteroatoms selected from N, O, S.

In particular, this modulator can be a compound, wherein

-   -   R₁ is hydrogen, ethynyl, chloro or bromo,    -   X is CH═CH or S,    -   Y is a group of formula (II), wherein        -   the N-containing ring system is optionally annelated with            cyclopropyl, cyclopentyl or phenyl,        -   n is 1 or 2,        -   R₂ is (C₁₋₈)alkyl, (C₁₋₄)alkylamino,            di(C₁₋₄)alkylamino(C₁₋₄)alkyl, (C₁₋₄)alkoxy,            (C₁₋₄)alkoxy(C₁₋₄)alkyl or        -   a group (CH₂)_(m)-Z, wherein Z is unsubstituted cyclohexyl,            unsubstituted phenyl, phenyl substituted by (C₁₋₄)alkoxy,            phenyl substituted by heterocyclyl having 6 ring members and            1 or 2 heteroatoms selected from N, O, or        -   unsubstituted or substituted heterocyclyl having 6 ring            members and 1 or 2 heteroatoms selected from N, O;    -   m is 1 or 2,    -   R₃ is hydrogen or (C₁₋₄)alkoxy.

In another embodiment of such a modulator, Y can be a group of formula(II), wherein

-   -   the N-containing ring system is optionally annelated with        cyclopropyl, cyclopentyl or phenyl,    -   R₂ is methyl, dimethylaminoethyl, methoxyethyl, or    -   a group (CH₂)_(m)-Z, wherein Z is unsubstituted cyclohexyl,        unsubstituted phenyl, phenyl substituted by methoxy, piperazinyl        or morpholinyl;    -   pyridinyl, piperidinyl, tetrahydrofuranyl, unsubstituted        piperazinyl or piperazinyl substituted by methyl or phenyl,

and m, n, R₁, R₃ and X are as defined above.

The compounds of the invention can be in the form of a salt and/or foruse as a pharmaceutical. The present invention hence also relates to apharmaceutical composition comprising a compound as describedherein-above in association with at least one pharmaceutical excipient,and to a method of treating disorders mediated by kallikrein-7 activity,which treatment comprises administering to a subject in need of suchtreatment an effective amount of a compound of the invention.

According to the present invention, a disorder which is mediated bykallikrein-7 activity can be selected from the group consisting ofinflammatory and/or hyperpoliferative and pruritic skin diseases such askeloids, hypertrophic scars, acne, atopic dermatitis, psoriasis,pustular psoriasis, rosacea, Netherton's syndrome or other pruriticdermatoses such as prurigo nodularis, unspecified itch of the elderly aswell as other diseases with epithelial barrier dysfunction such as agedskin, inflammatory bowel disease and Crohn's disease, as well aspancreatitis, or of cancer, in particular ovarian cancer.

DETAILED DESCRIPTION OF THE INVENTION

List of abbreviations Abbreviation Description DMSO dimethylsulfoxidehK7 human kallikrein 7 UTR untranslated region LEKTI lympho-epithelialKazal-type related inhibitor Spink5 serine protease inhibitor Kazal-type5 ALP antileukoprotease HPLC high performance liquid chromatographyGluHCl glucosamine hydrochloride pro-hK7 pro-human kallikrein 7 PEGpolyethylene glycol SDS sodium dodecyl sulfate Tristris-(hydroxymethyl)-amino methane IPTG isopropyl-β-D-thiogalactosideGSH Glutathion or γ-L-Glutamyl-L-cysteinylglycin GSSH oxidized form ofglutathion EDTA ethylenediaminetetraacitic acid DMSO dimethylsulfoxideHCl hydrochloric acid SLS Swiss Light Source a.u. asymmetric unit DTTD,L-dithiothreitol

Kallikrein 7 is a S1 serine protease of the kallikrein gene familydisplaying a chymotrypsin like activity. Human kallikrein 7 (hK7, KLK7or stratum corneum chymotryptic enzyme (SCCE), Swissprot P49862) playsan important role in skin physiology (1, 2, 3).

The present invention provides a crystal of human kallikrein 7comprising the binding pocket having a three-dimensional structurecharacterized by the structure coordinates of Table 3 below. The presentinvention also provides to a computer readable medium comprising datastorage material encoded with computer readable data wherein said datacomprises the structure coordinates of a crystal according to theinvention, and the use of this crystal for the generation of crystalstructure data. Moreover, the present invention provides a method ofidentifying a ligand that binds to kallikrein 7, this method comprisingthe steps of (i) using the three dimensional structure data generatedaccording to the invention to select and/or design a potential ligandthat binds to kallikrein 7, and (ii) identifying among the potentialligand selected in step (i), those ligands that bind to kallikrein 7 inan in vitro, in vivo or cell-based assay. Modulator of kallikrein 7according to the present invention are characterised in that it binds inthe binding pocket having a three-dimensional structure characterized bythe structure coordinates of Table 3 and can be a compound of formula

wherein

-   -   R₁ is hydrogen, cyano, (C₁₋₈)alkyl, (C₂₋₈)alkenyl,        (C₂₋₈)alkynyl, halogen, (C₁₋₈)alkylamino,        (C₁₋₈)alkylamino(C₁₋₈)alkyl, (C₁₋₈)alkoxy, halo(C₁₋₈)alkyl,    -   X is CH═CH, NH, N═CH, O or S,    -   Y is a group of formula

-   -   wherein        -   the N-containing ring system is optionally annelated with            (C₃₋₈)cycloalkyl, (C₆₋₁₈)aryl or heterocyclyl having 5 to 6            ring members and 1 to 4 heteroatoms selected from N, O, S,        -   n is 1, 2 or 3,        -   R₂ is            -   (C₁₋₈)alkyl, (C₁₋₈)alkylamino,                (C₁₋₈)alkylamino(C₁₋₈)alkyl,                di(C₁₋₈)alkylamino(C₁₋₈)alkyl, halo(C₁₋₈)alkyl,                (C₁₋₈)alkoxy, (C₁₋₈)alkoxy(C₁₋₈)alkyl, or            -   (CH₂)_(m)-Z, wherein Z is unsubstituted or substituted                (C₃₋₈)cycloalkyl, (C₈₋₁₈)aryl or heterocyclyl having 5                to 6 ring members and 1 to 4 heteroatoms selected from                N, O, S and m is 0, 1 or 2,        -   R₃ is hydrogen, (C₁₋₈)alkyl, (C₁₋₈)alkoxy, (C₆₋₁₈)aryl or            heterocyclyl having 5 to 6 ring members and 1 to 4            heteroatoms selected from N, O, S.

The crystals according to the invention preferably belong to theorthorhombic space group P2₁2₁2₁ (triclinic). The crystals have 1molecule per asymmetric unit.

Depending on the conditions used for crystallization, the parameterscharacterising the unit cell may vary with a limited range, at leastwithin the range of the resolution. The resolution of the X-raycrystallography is typically≦5 Angstroms and by means of thepurification method described therein, it is possible to providecrystals of such high internal order that a resolution of ≦2 Å can beachieved.

The term “unit cell” refers to the basic shape block. The entire volumeof a crystal may be constructed by regular assembly of such blocks. Eachunit cell comprises a complete representation of the unit of pattern,the repetition of which builds up the crystal.

The term “space group” according to the invention refers to thearrangement of symmetry elements of a crystal.

The term “structure coordinates” or “atomic coordinates” refers tomathematical coordinates derived from the mathematical equations relatedto the pattern obtained on diffraction of a monochromatic beam of X-raysby the atoms (scattering centers) of a crystal comprising hK7. Thediffraction data are used to calculate an electron density map of therepeating unit of the crystal. The electron density maps are used toestablish the positions of the individual atoms within the unit cell ofthe crystal. The structure coordinates of hK7 can be found in Table 3.

A “fragment” of Kallikrein 7 comprises more than 50% consecutive aminoacids of the sequence of the Kallikrein 7.

As used herein, a “homologue” of that sequence shares at least 70%identity, preferably 80% identity, more preferably 90%, and even morepreferably 95% identity with the corresponding sequence when performingoptimal alignment. Optimal alignment of sequences for determining acomparison window may be conducted by the local homology algorithm ofSmith and Waterman (J. Theor. Biol., 91 (2) pgs. 370-380 (1981), by thehomology alignment algorithm of Needleman and Wunsch, J. Miol. Biol.,48(3) pgs. 443-453 (1972), by the search for similarity via the methodof Pearson and Lipman, PNAS, USA, 85(5) pgs. 2444-2448 (1988) or bycomputerized implementations of these algorithms (GAP, BESTFIT, FASTAand TFASTA in the Wisconsin Genetics Software Package Release 7.0,Genetic Computer Group, 575, Science Drive, Madison, Wis.).

The best alignment (i.e., resulting in the highest percentage ofidentity over the comparison window) generated by the various methods isselected for determining percentage identity.

The terms “ligand” or “modulator”, which are used interchangeablyherein, refers to a molecule or group of molecules that bind to one ormore specific sites of Kallikrein 7. A ligand according to the inventioncan be an agonist or an antagonist. In addition, ligands according tothe invention are preferably low molecular weight molecules.

The term “low molecular weight molecules” according to the inventionrefers to preferably organic compounds generally having a molecularweight less than about 1000, more preferably less than about 500.

More preferably, said ligand inhibits kallikrein 7 biological activity.A compound is considered as an kallikrein 7 inhibitor if it has an IC₅₀ranging from 0.001 nM to 1.0 μM.

Preferred modulators are organic compounds, e.g. 1,2-dicarboxylic acidamides of an N-containing ring system, such as e.g. pyrrolidine, e.g.which are antagonists of Kallikrein-7 activity.

In one aspect the present invention is a compound of formula

whereinR₁ is hydrogen, cyano, alkyl, alkenyl, alkynyl, halogen, alkylamino,alkylaminoalkyl, alkoxy, haloalkyl,

X is CH═CH, NH, N═CH, O or S,

Y is a group of formula

wherein

-   -   the N-containing ring system is optionally annelated with        cycloalkyl, aryl or heterocyclyl having 5 to 6 ring members and        1 to 4 heteroatoms selected from N, O, S,    -   n is 1, 2 or 3,    -   R₂ is        -   alkyl, alkylamino, alkylaminoalkyl, dialkylaminoalkyl,            haloalkyl, alkoxy, alkoxyalkyl, or        -   (CH₂)_(m)-Z, wherein Z is unsubstituted or substituted            cycloalkyl, aryl or heterocyclyl having 5 to 6 ring members            and 1 to 4 heteroatoms selected from N, O, S and m is 0, 1            or 2,    -   R₃ is hydrogen, alkyl, alkoxy, aryl or heterocyclyl having 5 to        6 ring members and 1 to 4 heteroatoms selected from N, O, S.

Any group (substituent) defined herein may comprise 1 to 18 carbonatoms, for example

-   -   alkyl e.g. includes (C1-12)alkyl, such as (C1-4)alkyl, e.g.        methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl,        sec-butyl, n-pentyl, neopentyl, n-hexyl;        -   alkenyl e.g. includes (C2-12)alkenyl, such as ethenyl,            propenyl, butenyl, 1-methyl-2-buten-1-yl, alkadienes and the            like;        -   alkynyl e.g. includes (C2-12)alkynyl, such as ethynyl;        -   cycloalkyl e.g. includes (C3-12)cycloalkyl, such as            cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;        -   alkoxy e.g. includes (C1-12)alkoxy, such as methoxy, ethoxy;        -   aryl includes (C₆₋₁₈)aryl, e.g. phenyl, naphtyl;        -   aliphatic heterocyclyl and armoatic heterocyclyl;        -   heterocyclyl having 1 to 4 heteroatoms selected from N, O,            S; such as heterocyclyl            having    -   1 to 2 heteroatoms selected from N, O, e.g. including    -   pyridinyl, e.g. pyridin-3-yl, pyridin-4-yl;    -   piperidinyl, e.g. piperidin-4-yl;    -   piperazinyl, e.g. piperazin-1-yl;    -   morpholinyl, e.g. morpholin-4-yl;    -   tetrahydrofuranyl, e.g. tetrahydrofuran-2-yl;    -   halogen includes F, Cl, Br, I, such as chloro, bromo;

Any group defined herein may be unsubstituted or substituted, e.g. oneor morefold.

Substituents include e.g. methyl, methoxy, ethynyl, chloro, bromo.

Alkyl, alkenyl, alkynyl, aryl and heterocyclyl include unsubstituted orsubstituted alkyl, aryl or heterocyclyl, e.g. substituted by groupswhich are conventional in organic chemistry.

In one aspect the present invention is a compound of formula (I) asdefined above, wherein

R₁ is hydrogen, cyano, (C₂₋₈)alkenyl, (C₂₋₈)alkynyl or halogen

X is CH═CH, NH, N═CH, O or S,

Y is a group of formula

wherein

-   -   the N-containing ring system is optionally annelated with        (C₃₋₈)cycloalkyl, (C₆₋₁₈)aryl or heterocyclyl having 5 to 6 ring        members and 1 to 2 heteroatoms selected from N, O, S,    -   n is 1, 2 or 3,    -   R₂ is        -   (C₁₋₈)alkyl, (C₁₋₈)alkylamino, (C₁₋₈)alkylamino(C₁₋₈)alkyl,            di(C₁₋₈)alkylamino(C₁₋₈)alkyl, (C₁₋₈)alkoxy,            (C₁₋₈)alkoxy(C₁₋₈)alkyl, or        -   (CH₂)_(m)-Z, wherein Z is unsubstituted or substituted            (C₃₋₈)cycloalkyl, (C₈₋₁₈)aryl or heterocyclyl having 5 to 6            ring members and 1 to 2 heteroatoms selected from N, O, S            and m is 1 or 2,    -   R₃ is hydrogen, (C₁₋₈)alkyl or (C₁₋₈)alkoxy.

In one aspect the present invention is a compound of formula (I),wherein

-   -   R₁ is hydrogen, ethynyl, chloro or bromo,    -   X is CH═CH or S,    -   Y is a group of formula (II), wherein        -   the N-containing ring system is optionally annelated with            cyclopropyl, cyclopentyl or phenyl,        -   n is 1 or 2,        -   R₂ is (C₁₋₈)alkyl, (C₁₋₄)alkylamino,            di(C₁₋₄)alkylamino(C₁₋₄)alkyl, (C₁₋₄)alkoxy,            (C₁₋₄)alkoxy(C₁₋₄)alkyl or        -   a group (CH₂)_(m)-Z, wherein Z is unsubstituted cyclohexyl,            unsubstituted phenyl, phenyl substituted by (C₁₋₄)alkoxy,            phenyl substituted by heterocyclyl having 6 ring members and            1 or 2 heteroatoms selected from N, O, or unsubstituted or            substituted heterocyclyl having 6 ring members and 1 or 2            heteroatoms selected from N, O;        -   m is 1 or 2,        -   R₃ is hydrogen or (C₁₋₄)alkoxy.

In one aspect the present invention is a compound of formula (I) and Yis a group of formula (II), wherein

-   -   the N-containing ring system is optionally annelated with        cyclopropyl, cyclopentyl or phenyl,    -   R₂ is methyl, dimethylaminoethyl, methoxyethyl, or    -   a group (CH₂)_(m)-Z, wherein Z is unsubstituted cyclohexyl,        unsubstituted phenyl, phenyl substituted by methoxy, piperazinyl        or morpholinyl; pyridinyl, piperidinyl, tetrahydrofuranyl,        unsubstituted piperazinyl or piperazinyl substituted by methyl        or phenyl,    -   and m, n, R₁, R₃ and X are as defined above.

In one aspect the present invention is a compound of formula (I),wherein

X is CH═CH,

R₁ is ethynyl or chloro,Y is a group of formula (II), whereinn is 1,R₃ is hydrogen,R₂ is methyl, methoxyethyl, dimethylaminoethyl, pyridin-3-ylmethyl,pyridin-4-ylmethyl, pyridin-3-yl-ethyl, pyridin-4-yl-ethyl,6-methoxy-pyridin-3-ylmethyl, (4-methoxy-phenyl)-ethyl,(4-methyl-piperazin-1-yl)-ethyl, (4-benzyl-piperazin-1-yl)-ethyl,4-(4-methyl-piperazin-1-yl)-benzyl, 1-methyl-piperidin-4-ylmethyl,2-(4-morpholin-4-ylmethyl)-benzyl.

In one aspect the present invention is a compound of formula (I),wherein

X is CH═CH,

R₁ is hydrogen,Y is a group of formula (II), whereinThe N-containing ring system is optionally annelated with phenyl,R₃ is hydrogen or phenyl,n is 1 or 2,R₂ is benzyl, phenethyl, cyclohexylmethyl, (4-methoxy-phenyl)-ethyl,3-methyl-butyl, tetrahydrofuran-2-ylmethyl.

In one aspect the present invention is a compound of formula (I),wherein

X is CH═CH,

R₁ is ethynyl,Y is a group of formula (II), whereinThe N-containing ring system is optionally annelated with cyclopropyl,cyclopentyl, phenyl,R₃ is hydrogen,n is 1,R₂ is pyridin-3-ylmethyl.

In one aspect the present invention is a compound of formula (I),wherein

X is CH═CH

R₁ is ethynyl,Y is a group of formula (II), whereinR₃ is methoxy,n is 1,R₂ is pyridin-3-ylmethyl.

In one aspect the present invention is a compound of formula (I),wherein

X is CH═CH

R₁ is ethynyl,Y is a group of formula (II), whereinR₃ is hydrogen,n is 2,R₂ is pyridin-3-ylmethyl.

In one aspect the present invention is a compound of formula (I),wherein

X is S

R₁ is chloro or bromo,Y is a group of formula (II), whereinR₃ is hydrogen,n is 1,R₂ is (4-methoxy-phenyl)-ethyl.

In a compound of formula I each single defined substitutent may be apreferred substituent, e.g. independently of each other substitutentdefined.

In another aspect the present invention provides a compound of formulaI, selected from the group consisting of

-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(2-pyridin-3-yl-ethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    2-[(2-dimethylamino-ethyl)-amide]    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(2-pyridin-4-yl-ethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(6-methoxy-pyridin-3-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(1-methyl-piperidin-4-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[4-(4-methyl-piperazin-1-yl)-benzylamide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-(4-morpholin-4-ylmethyl-benzylamide),-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide] 2-methylamide,-   (S)-Pyrrolidine-1,2-dicarboxylic acid    2-{[2-(4-benzyl-piperazin-1-yl)-ethyl]amide}    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(2-methoxy-ethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-4-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-{[2-(4-methyl-piperazin-1-yl)-ethyl]-amide},-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(6-chloro-naphthalen-1-ylmethyl)-amide]    2-{[2-(4-methoxy-phenyl)-ethyl]-amide},-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-chloro-naphthalen-1-ylmethyl)-amide]    2-{[2-(4-methoxy-phenyl)-ethyl]-amide},-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(5-bromo-benzo[b]thiophen-3-ylmethyl)-amide]    2-{[2-(4-methoxy-phenyl)-ethyl]-amide},-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(5-chloro-benzo[b]thiophen-3-ylmethyl)-amide]    2-{[2-(4-methoxy-phenyl)-ethyl]-amide},-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-{[2-(4-methoxy-phenyl)-ethyl]-amide},-   (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide],-   (S)-Piperidine-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide],-   (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid    2-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    1-[(pyridin-3-ylmethyl)-amide],-   (S)-2,3-Dihydro-indole-1,2-dicarboxylic acid    1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide],-   (S)-1,3-Dihydro-isoindole-1,2-dicarboxylic acid    2-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    1-[(pyridin-3-ylmethyl)-amide],-   (1R,2S,5S)-3-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid    3-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide],-   (1S,2S,5R)-3-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid    3-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(naphthalen-1-ylmethylyamide] 2-(phenethyl-amide),-   (2S,4S)-4-Phenyl-pyrrolidine-1,2-dicarboxylic acid    1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide),-   (2S,4R)-4-Phenyl-pyrrolidine-1,2-dicarboxylic acid    1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide),-   (S)-3,4-Dihydro-1H-isoquinoline-2,3-dicarboxylic acid    2-[(naphthalen-1-ylmethylyamide] 3-(phenethyl-amide),-   (S)-Piperidine-1,2-dicarboxylic acid    1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide),-   (S)-Pyrrolidine-1,2-dicarboxylic acid    2-{[2-(4-methoxy-phenyl)-ethyl]-amide}    1-[(naphthalen-1-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid 2-benzylamide    1-[(naphthalen-1-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid 2-cyclohexylmethyl-amide    1-[(naphthalen-1-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid 2-[(3-methyl-butyl)-amide]    1-[(naphthalen-1-ylmethyl)-amide],-   (S)-Pyrrolidine-1,2-dicarboxylic acid    1-[(naphthalen-1-ylmethyl)-amide]    2-[(tetrahydro-furan-2-ylmethyl)-amide],-   (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid    3-[(7-chloro-naphthalen-1-ylmethyl)-amide]    2-[(pyridin-3-ylmethyl)-amide], and-   (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid    3-[(7-chloro-naphthalen-1-ylmethyl)-amide]    2-{[2-(4-methoxy-phenyl)-ethyl]-amide}.

The chemical names of the compounds of the present invention asindicated herein are copied from ISIS, version 2.5 (AutoNom 2000 Name).

Compounds provided by the present invention are hereinafter designatedas “compound(s) of (according to) the present invention”. A compound ofthe present invention includes a compound in any form, e.g. in freeform, in the form of a salt, in the form of a solvate and in the form ofa salt and a solvate.

In another aspect the present invention provides a compound of thepresent invention in the form of a salt.

Such salts include preferably pharmaceutically acceptable salts,although pharmaceutically unacceptable salts are included, e.g. forpreparation/isolation/purification purposes.

A compound of the present invention in free form may be converted into acorresponding compound in the form of a salt; and vice versa. A compoundof the present invention in free form or in the form of a salt and inthe form of a solvate may be converted into a corresponding compound infree form or in the form of a salt in non-solvated form; and vice versa.

A compound of the present invention may exist in the form of isomers andmixtures thereof; e.g. optical isomers, diastereoisomers, cis/transconformers. A compound of the present invention may e.g. containasymmetric carbon atoms and may thus exist in the form of enantiomers ordiastereoisomers and mixtures thereof, e.g. racemates. A compound of thepresent invention may be present in the (R)-, (S)- or(R,S)-configuration preferably in the (R)- or (S)-configurationregarding specified positions in the compound of the present invention.

A compound provided by the present invention may be in the (R)- and inthe (S)-configuration, e.g. including mixtures thereof, in a compound offormula I, and is preferably in the (R)- or in the (S)-configuration.

Isomeric mixtures may be separated as appropriate, e.g. according, e.g.analogously, to a method as conventional, to obtain pure isomers. Thepresent invention includes a compound of the present invention in anyisomeric form and in any isomeric mixture.

The present invention also includes tautomers of a compound of thepresent invention, where tautomers can exist.

In another aspect the present invention provides a process for theproduction of a compound of the present invention, e.g. of formula I,comprising the steps

A. Reacting a Compound of Formula

wherein R₁ and R₃ are as defined above, with a compound of formula

R₂—NH₂  (IV)

wherein R₂ is as defined above, under appropriate conditions, e.g. inthe presence of N-(3-dimethylamino-propyl)-N-carbodiimide-HCl,N,N-diisopropylethylamine, CH₂Cl₂, trifluoroacetic acid, acetonitril, atappropriate temperatures, e.g. room temperature, for an appropriatetime, e.g. over night; OR

B) Reacting a Compound of Formula

wherein R₂, R₃ and n are as defined above, with a compound of formula

wherein R₁ and X are as defined above, under appropriate conditions,e.g. in the presence of 4-nitrophenylchloroformate, pyridine,N,N-diisopropylethylamine, CH₂Cl₂, at appropriate temperatures, e.g.room temperature, for an appropriate time, e.g. over night; andisolating a compound of formula I obtained from the reaction mixture.

In an intermediate of formulae (III), (IV), (V) or (VI) (startingmaterials), functional groups, if present, optionally may be inprotected form or in the form of a salt, if a salt-forming group ispresent. Protecting groups, optionally present, may be removed at anappropriate stage, e.g. according, e.g. analogously, to a method asconventional

A compound of formula I thus obtained may be converted into anothercompound of formula I, e.g. or a compound of formula I obtained in freeform may be converted into a salt of a compound of formula I and viceversa.

Intermediates (starting materials) of formulae (III), (IV), (V) or (VI)are known or may be prepared according, e.g. analogously, to a method asconventional or as specified herein.

Any compound described herein, e.g. a compound of the present inventionand intermediates of formulae (III), (IV), (V) or (VI) may be preparedas appropriate, e.g. according, e.g. analogously, to a method asconventional, e.g. or as specified herein.

The compounds of the present invention, e.g. including a compound offormula I, exhibit pharmacological activity and are therefore useful aspharmaceuticals. E.g., the compounds of the present invention are foundto inhibit Kallikrein-7 activity.

Compounds of the present invention have IC₅₀ values between 1 nM and 10μM e.g. determined in the following assay:

Materials and Buffers

The fluorescence-quenched substrateAc-Glu-Asp(EDANS)-Lys-Pro-Ile-Leu-PhêArg-Leu-Gly-Lys(DABCYL)-Glu-NH₂(where ̂ indicates the scissile bond, identified by MS analysis) ispurchased from Biosyntan (Berlin, Germany) and kept as a 5 mM stocksolution in DMSO at −20° C. All other chemicals are of analytical grade.

Enzymatic reactions are conducted in 50 mM sodium citrate buffer at pH5.6 containing 150 mM NaCl and 0.05% (w/v) CHAPS.

All protein and peptide containing solutions are handled in siliconizedtubes (Life Systems Design, Merenschwand, Switzerland). The compoundsolutions as well as the enzyme and the substrate solutions aretransferred to the 384-well plates (black Cliniplate; cat. no. 95040020Labsystems Oy, Finland) by means of a CyBi-Well 96-channel pipettor(CyBio AG, Jena, Germany).

Instrumentation for FI measurements

For fluorescence intensity (FI) measurements an Ultra Evolution reader(TECAN, Maennedorf, Switzerland) is used. The instrument is equippedwith a combination of a 350 nm (20 nm bandwidth) and a 500 nm (25 nmbandwidth) bandpath filter for fluorescence excitation and emissionacquisition, respectively. To increase the signal:background ratio, anappropriate dichroic mirror is employed. The optical filters and thedichroic mirror are purchased from TECAN. The fluorophores in each wellare excited by three flashes per measurement.

Determination of IC₅₀ Values

For the determination of IC₅₀ values the assay is performed at roomtemperature in 384-well plates. All final assay volumes were 30 μl. Testcompounds are dissolved in 90% (v/v) DMSO/water and diluted in water(containing 0.05% (w/v) CHAPS) to 3-times the desired assayconcentration. The 11 final compound concentrations are: 0.3 nM, 1 nM, 3nM, 10 nM, 30 nM, 100 nM, 300 nM, 1 μM, 3 μM, 10 μM and 30 μM. For eachassay, 10 μl water/CHAPS (±test compound) are added per well, followedby 10 μl protease solution (diluted with 1.5× assay buffer). Theprotease concentration in final assay solution is 0.2 nM (according tothe enzyme concentrations determined by the Bradford method). After 1hour of incubation at room temperature, the reaction is started byaddition of 10 μl substrate solution (substrate dissolved in 1.5× assaybuffer, final concentration was 2 μM). The effect of the compound on theenzymatic activity is obtained from the linear progress curves anddetermined from two readings, the first one taken directly after theaddition of substrate and the second one after 1 hour. The IC₅₀ value iscalculated from the plot of percentage of inhibition vs. inhibitorconcentration using non-linear regression analysis software (XLfit,Vers. 4.0; ID Business Solution Ltd., Guildford, Surrey, UK).

The compounds of the present invention show activity in that ASSAY andare therefore indicated for the treatment of disorders (diseases)mediated by Kallikrein-7 activity. IC₅₀ values for compounds of thepresent invention are in the range of below 10 μM, preferably below 10nM, e.g. the compound of example 36 has an IC₅₀ value of 3 nM.

Disorders, e.g. including diseases, mediated by Kallikrein-7 activityand which are prone to be successfully treated with Kallikrein-7antagonists, e.g. with compounds of the present invention, includedisorders, wherein the activity of Kallikrein-7 play a causal orcontributory role, e.g. diseases involved with epithelial dysfunctionsuch as inflammatory and/or hyperproliferative and pruritic skindiseases like e.g. atopic dermatitis, psoriasis, Netherton syndrome orother pruritic dermatoses such as prurigo nodularis, unspecified itch aswell as other diseases with epithelial barrier dysfunction such asinflammatory bowel disease or Crohn's disease.

In another aspect the present invention provides

-   -   a compound of the present invention for use as a pharmaceutical,    -   the use of a compound of the present invention as a        pharmaceutical,    -   the use of a compound of the present invention for the        manufacture of a medicament, e.g. for the treatment of disorders        mediated by Kallikrein-7 activity.

For pharmaceutical use one or more compounds of the present inventionmay be used, e.g. one, or a combination of two or more compounds of thepresent invention, preferably one compound of the present invention isused.

A compound of the present invention may be used as a pharmaceutical inthe form of a pharmaceutical composition.

In another aspect the present invention provides a pharmaceuticalcomposition comprising a compound of the present invention inassociation with at least one pharmaceutically acceptable excipient,e.g. appropriate carrier and/or diluent, e.g. including fillers,binders, disintegrants, flow conditioners, lubricants, sugars orsweeteners, fragrances, preservatives, stabilizers, wetting agentsand/or emulsifiers, solubilizers, salts for regulating osmotic pressureand/or buffers.

In another aspect the present invention provides

-   -   a pharmaceutical composition of the present invention for use of        treating disorders which are mediated by Kallikrein-7 activity.    -   the use of a pharmaceutical composition of the present invention        for treating disorders which are mediated by Kallikrein-7        activity.

In a further aspect the present invention provides a method of treatingdisorders which are mediated by Kallikrein-7 activity, e.g. includingdisorders as specified above, which treatment comprises administering toa subject in need of such treatment an effective amount of a compound ofthe present invention; e.g. in the form of a pharmaceutical composition.

In another aspect the present invention provides

-   -   a compound of the present invention for the manufacture of a        medicament,    -   the use of a compound of the present invention for the        manufacture of a medicament, e.g. a pharmaceutical composition,        for the treatment of disorders, which are mediated by        Kallikrein-7 activity, e.g. for the treatment of skin diseases        like e.g. atopic dermatitis, psoriasis, Netherton syndrome or        other pruritic dermatoses such as prurigo nodularis, unspecified        itch.

Treatment includes treatment and prophylaxis (prevention). Treatment canbe by local or systemic application such as e.g. creams, ointments orsuppositories or by oral, sc or iv application, respecitvely.

For such treatment, the appropriate dosage will, of course, varydepending upon, for example, the chemical nature and the pharmakokineticdata of a compound of the present invention used, the individual host,the mode of administration and the nature and severity of the conditionsbeing treated. However, in general, for satisfactory results in largermammals, for example humans, an indicated daily dosage includes a range

-   -   from about 0.001 g to about 1.5 g, such as 0.001 g to 1.5 g;    -   from about 0.01 mg/kg body weight to about 20 mg/kg body weight,        such as 0.01 mg/kg body weight to 20 mg/kg body weight,        for example administered in divided doses up to four times a        day.

A compound of the present invention may be administered to largermammals, for example humans, by similar modes of administration thanconventionally used with other mediators, e.g. low molecular weightinhibitors, of Kallikrein-7 activity.

A compound of the present invention may be administered by anyconventional route, for example enterally, e.g. including nasal, buccal,rectal, oral, administration; parenterally, e.g. including intravenous,intraarterial, intramuscular, intracardiac, subcutanous, intraosseousinfusion, transdermal (diffusion through the intact skin), transmucosal(diffusion through a mucous membrane), inhalational administration;topically; e.g. including epicutaneous, intranasal, intratrachealadministration; intraperitoneal (infusion or injection into theperitoneal cavity); epidural (peridural) (injection or infusion into theepidural space); intrathecal (injection or infusion into thecerebrospinal fluid); intravitreal (administration via the eye); e.g. inform of coated or uncoated tablets, capsules, (injectable) solutions,infusion solutions, solid solutions, suspensions, dispersions, soliddispersions; e.g. in the form of ampoules, vials, in the form of creams,gels, pastes, inhaler powder, foams, tinctures, lip sticks, drops,sprays, or in the form of suppositories. Preferably a compound of thepresent invention is applied topically.

For topical use, e.g. including administration to the eye, satisfactoryresults may be obtained with local administration of a 0.5-10%, such as1-3% concentration of active substance several times daily, e.g. 2 to 5times daily.

The compounds of the present invention may be administered in the formof a pharmaceutically acceptable salt, or in free form; optionally inthe form of a solvate. A compound of the present invention in the formof a salt and/or in the form of a solvate exhibit the same order ofactivity as a compound of the present invention in free form.

A compound of the present invention may be used for any method or use asdescribed herein alone or in combination with one or more, at least one,other, second drug substance.

In another aspect the present invention provides

-   -   A combination of a compound of the present invention with at        least one second drug substance;    -   A pharmaceutical combination comprising a compound of the        present invention in combination with at least one second drug        substance;    -   A pharmaceutical composition comprising a compound of the        present invention in combination with at least one second drug        substance and one or more pharmaceutically acceptable        excipient(s);    -   A compound of the present invention in combination with at least        one second drug substance, e.g. in the form of a pharmaceutical        combination or composition, for use in any method as defined        herein, e.g.        -   A combination, a pharmaceutical combination or a            pharmaceutical composition, comprising a compound of the            present invention and at least one second drug substance for            use as a pharmaceutical;    -   The use as a pharmaceutical of a compound of the present        invention in combination with at least one second drug        substance, e.g. in the form of a pharmaceutical combination or        composition;    -   The use of a compound of the present invention for the        manufacture of a medicament for use in combination with a second        drug substance    -   A method for treating disorders mediated by Kallikrein-7        activity in a subject in need thereof, comprising        co-administering, concomitantly or in sequence, a        therapeutically effective amount of a compound of the present        invention and at least one second drug substance, e.g. in the        form of a pharmaceutical combination or composition;    -   A compound of the present invention in combination with at least        one second drug substance, e.g. in the form of a pharmaceutical        combination or composition, for use in the preparation of a        medicament for use in disorders mediated by Kallikrein-7        activity.

Combinations include fixed combinations, in which a compound of thepresent invention and at least one second drug substance are in the sameformulation; kits, in which a compound of the present invention and atleast one second drug substance in separate formulations are provided inthe same package, e.g. with instruction for co-administration; and freecombinations in which a compound of the present invention and at leastone second drug substance are packaged separately, but instruction forconcomitant or sequential administration are given.

In another aspect the present invention provides

-   -   A pharmaceutical package comprising a first drug substance which        is a compound of the present invention and at least one second        drug substance, beside instructions for combined administration;    -   A pharmaceutical package comprising a compound of the present        invention beside instructions for combined administration with        at least one second drug substance;    -   A pharmaceutical package comprising at least one second drug        substance beside instructions for combined administration with a        compound of the present invention.

Treatment with combinations according to the present invention mayprovide improvements compared with single treatment.

In another aspect the present invention provides

-   -   A pharmaceutical combination comprising an amount of a compound        of the present invention and an amount of a second drug        substance, wherein the amounts are appropriate to produce a        synergistic therapeutic effect;    -   A method for improving the therapeutic utility of a compound of        the present invention comprising co-administering, e.g.        concomitantly or in sequence, of a therapeutically effective        amount of a compound of the present invention and a second drug        substance.    -   A method for improving the therapeutic utility of a second drug        substance comprising co-administering, e.g. concomitantly or in        sequence, of a therapeutically effective amount of a compound of        the present invention and a second drug substance.

A combination of the present invention and a second drug substance as acombination partner may be administered by any conventional route, forexample as set out above for a compound of the present invention. Asecond drug may be administered in dosages as appropriate, e.g. indosage ranges which are similar to those used for single treatment, or,e.g. in case of synergy, even below conventional dosage ranges.

Pharmaceutical compositions according to the present invention may bemanufactured according, e.g. analogously, to a method as conventional,e.g. by mixing, granulating, coating, dissolving or lyophilizingprocesses. Unit dosage forms may contain, for example, from about 0.1 mgto about 1500 mg, such as 1 mg to about 1000 mg.

Pharmaceutical compositions comprising a combination of the presentinvention and pharmaceutical compositions comprising a second drug asdescribed herein, may be provided as appropriate, e.g. according, e.g.analogously, to a method as conventional, or as described herein for apharmaceutical composition of the present invention.

By the term “second drug substance” is meant an anti-inflammatory,immunomodulatory drug, anticancer drug, anesthetic drug orchemotherapeutic drug. A “second drug substance” can also be a compoundhaving Kallikrein-7 activity, but not being a compound of the presentinvention.

If the compounds of the present invention are administered incombination with other drugs dosages of the co-administered second drugwill of course vary depending on the type of co-drug employed, on thespecific drug employed, on the condition being treated, as in case of acompound of the present invention. In general dosages similar than thoseas provided by the second drug supplier may be appropriate

In the following Examples all temperatures indicated are in degreeCelsius (°).

The following abbreviations are also used:

-   aq. aqueous-   Ac₂O acetic anhydride-   AcOH acetic acid-   CH₂Cl₂ dichloromethane-   DCE 1,2-dichloroethane-   DIPEA N,N-diisopropylethylamine-   DMA N,N-dimethylacetamide-   EtOAc ethylacetate-   HATU O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium    hexafluorophosphate-   NMP N-methylpyrrolidinone-   rt room temperature-   TFA trifluoroacetic acid-   THF tetrahydrofuran-   TLC thin layer chromatography-   TMOF trimethylorthoformate

A kallikrein 7 inhibitor can also be a “peptide” or a “peptidederivative”, which terms are intended to embrace a “peptidomimetic” or“peptide analogue” which complement the three-dimensional structure ofthe binding pocket of kallikrein 7 or can be designed with improvedphysical or chemical properties to bind with the three-dimensionalbinding pocket of the kallikrein 7 as provided in the present invention.

The term “mutant” refers to a mutated sequence by deletion, insertion orpreferably replacement of one or more selected amino acids, providedthat such mutant sequence shares at least 90% identity, more preferably95%, and even more preferably 99% identity with the correspondingfragment sequence when performing optimal alignment. Methods for thepreparation of protein mutants are commonly known in the art. Forexample, kallikrein 7 mutants may be prepared by expression ofkallikrein 7 DNA previously modified in its coding region byoligonucleotide directed mutagenesis.

As used herein, the term “binding pocket” refers to the region ofkallikrein 7 that, as a result of its shape and physico-chemicalproperties favorably associates with another chemical entity or compoundand is defined in by the coordinates of Table 3.

The kallikrein 7 protein to be used for crystallization may bebiologically active or inactive. Such ability may be determined bymorphological, biochemical or viability analysis well-known in the art.

Expression of recombinant kallikrein 7 or fragment thereof is achievablein eukaryotic or prokaryotic systems or in vitro expression systems.

According to a preferred embodiment, kallikrein 7 is bound to at leastone ligand at any step prior to crystallization.

Kallikrein 7 may be expressed as a fusion protein, e.g. aglutathione-5-transferase (GST) or histidine-tagged fusion protein. Ifdesired, the fusion partner is removed before crystallization.

For carrying out the step of crystallization of the method for making acrystal, various methods can be used including vapour diffusion,dialysis or batch crystallization according to methods known in the art(“Crystallization of Biological Macromolecules”, A. McPherson, ColdSpring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA).

In vapour diffusion crystallization, a small volume (i.e., a fewmicroliters) of protein solution is mixed with a solution containing aprecipitant. This mixed volume is suspended over a well containing asmall amount, i.e. about 1 ml, of precipitant. Vapour diffusion from thedrop to the well will result in crystal formation in the drop.

The dialysis method of crystallization utilizes a semipermeablesize-exclusion membrane that retains the protein but allows smallmolecules (i.e. buffers and precipitants) to diffuse in and out. Indialysis, rather than concentrating the protein and the precipitant byevaporation, the precipitant is allowed to slowly diffuse through themembrane and reduce the solubility of the protein while keeping theprotein concentration fixed.

The batch method generally involves the slow addition of a precipitantto an aqueous solution of protein until the solution just becomesturbid, at this point the container can be sealed and left undisturbedfor a period of time until crystallization occurs. In the batchtechnique the precipitant and the target molecule solution are simplymixed. Supersaturation is achieved directly rather than by diffusion.Often the batch technique is performed under oil. The oil preventsevaporation and extremely small drops can be used. For this, the term“microbatch” is used. A modification of this technique is not to useparaffin oil (which prevents evaporation completely) but rather usesilicone oil or a mixture of silicone and paraffin oils so that a slowevaporation is possible.

The claimed invention can encompass any and all methods ofcrystallization. One skilled in the art can choose any of such methodsand vary the parameters such that the chosen method results in thedesired crystals.

One preferred method of crystallization of kallikrein 7 involves mixinga kallikrein 7 solution with a “reservoir buffer”. For crystalformation, the concentration of the precipitating agent in the mixturehas to be increased, e.g. by addition of precipitating agent, forexample by titration, or by allowing the concentration of precipitatingagent to balance by diffusion between the crystallization buffer and areservoir buffer (not necessarily the same as the original reservoirbuffer). Under suitable conditions such diffusion of precipitating agentoccurs along the gradient of precipitating agent, e.g. from thereservoir buffer having a higher concentration of precipitating agentinto the crystallization buffer having a lower concentration ofprecipitating agent. Diffusion may be achieved e.g. by vapour diffusiontechniques allowing diffusion of water in the common gas phase. Knowntechniques are e.g. vapour diffusion methods, such as the “hanging drop”or the “sitting drop” method. In the vapour diffusion method a drop ofcrystallization buffer containing the protein is hanging above orsitting beside a much larger pool of reservoir buffer. Alternatively,the balancing of the precipitating agent can be achieved through asemipermeable membrane that separates the crystallization buffer fromthe reservoir buffer and prevents dilution of the protein into thereservoir buffer.

Formation of kallikrein 7 can be achieved under various conditions whichare essentially determined by the following parameters: pH, presence ofsalts and additives, precipitating agent, protein concentration andtemperature. The pH may range, for example, from about 4.0 to 9.0.

In another specific embodiment, the invention relates to a method formaking a co-crystal of kallikrein 7 in complex with a ligand.

The crystal form of kallikrein 7 crystal may also be used for exchangingthe ligand by soaking compounds of interest, for example, for compoundoptimization, or for the discovery of novel scaffolds in fragment basedscreening approaches.

Structure coordinates of a crystalline composition of this invention maybe stored in a machine-readable form on a machine-readable storagemedium, e.g. a computer hard drive, diskette, DAT tape, etc., fordisplay as a three-dimensional shape or for other uses involvingcomputer-assisted manipulation of, or computation based on, thestructural coordinates or the three-dimensional structures they define.For example, data defining the three dimensional structure of a proteinof the kallikrein family, or portions or structurally similar homologuesof such proteins, may be stored in a machine-readable storage medium,and may be displayed as a graphical three-dimensional representation ofthe protein structure, typically using a computer capable of reading thedata from said storage medium and programmed with instructions forcreating the representation from such data.

According to the present invention, a three-dimensional kallikrein 7model is obtainable from a kallikrein 7 crystal comprising thekallikrein 7, fragment or homologue thereof.

The present invention also relates to a computer readable medium havingstored a model of the kallikrein 7 crystal structure. In a preferredembodiment, said model is built from all or a selected portion of it, ofthe atomic coordinates of Table 3 derived from the X-ray diffractiondata.

By “selected portion”, it is meant the structure coordinates of at least10 consecutive amino acids shown in Table 3 and preferably at least 50amino acids, and more preferably at least 100 consecutive amino acids.

The knowledge obtained from the three-dimensional model of kallikrein 7can be used in various ways. For example, it can be used to identifychemical entities, for example, small organic and bioorganic moleculessuch as peptidomimetics and synthetic organic molecules that bind tokallikrein 7 and preferably block or prevent a kallikrein 7-mediated orassociated process or event, or that act as kallikrein δ agonists.Furthermore, this information can be used to design and preparekallikrein 7 mutants, e.g. mutants with altered catalytic activity,model the three-dimensional structure and solve the crystal structure ofproteins, such as kallikrein 7 homologues, kallikrein 7 mutants orkallikrein 7 co-complexes, involving e.g. molecular replacement orhomology modeling.

The term “molecular replacement” refers to a method that involvesgenerating a preliminary structural model of a crystal whose structuralcoordinates are unknown, by orienting and positioning a molecule whosestructural coordinates are known, e.g., the kallikrein 7 coordinateswithin the unit cell of the unknown crystal, so as to best account forthe observed diffraction pattern of the unknown crystal. Phases can thenbe calculated from this model, and combined with the observed amplitudesto give an approximated Fourier synthesis of the structure whosecoordinates are unknown. This in turn can be subject to any of theseveral forms of refinement to provide a final accurate structure of theunknown crystal. Using the structural coordinates provided by thisinvention, molecular replacement may be used to determine the structuralcoordinates of a crystalline co complex, unknown ligand, mutant, orhomolog, or of a different crystalline form of kallikrein 7.Additionally, the claimed crystal and its coordinates may be used todetermine the structural coordinates of a chemical entity thatassociates with kallikrein 7.

“Homology modeling” according to the invention involves constructing amodel of an unknown structure using structural coordinates of one ormore related proteins, protein domains and/or one subdomains such askallikrein 7. Homology modeling may be conducted by fitting common orhomologous portions of the protein or peptide whose three dimensionalstructure is to be solved to the three dimensional structure ofhomologous structural elements. Homology modeling can include rebuildingpart or all of a three dimensional structure with replace of amino acidsor other components by those of the related structure to be solved.

Based on the three-dimensional structure of kallikrein 7 as provided inthe present invention and using the atomic coordinates of Table 3, or aselected portion of it, the effects of site-specific mutations can bepredicted. More specifically, the structural information provided hereinpermits the identification of desirable sites for amino acidmodification, particularly amino acid mutation resulting insubstitutional, insertional or deletional variants. Such variants may bedesigned to have special properties, particularly properties distinctfrom wild-type kallikrein 7, such as altered catalytic activity.Substitutions, deletions and insertions may be combined to arrive at adesired variant. Such variants can be prepared by methods well-known inthe art, e.g. starting from wild-type kallikrein 7 or by de novosynthesis.

The kallikrein 7 structural information provided herein is useful forthe design of ligands which are capable of selectively interacting withkallikrein 7, but not other proteases other than Kallikrein 7, andthereby specifically modulating the biological activity of kallikrein 7and not other kallikrein 7 proteases.

Chemical entities that have a surface that mimics the accessible surfaceof the binding pocket of kallikrein 7 can be constructed by thoseskilled in the art. By way of example, the skilled artisan can screenthree-dimensional structural databases of compounds to identify thosecompounds that position appropriate functional groups in similar threedimensional structural arrangement, then build combinatorial chemistrylibraries around such chemical entities to identify those with highaffinity to the binding pocket of kallikrein 7.

In a specific embodiment of the invention, a cell-based assay isdesigned to identify ligands which inhibit the biological activity ofkallikrein 7.

Ligands, such as small molecular weight compounds can be identified fromscreening compound databases or libraries and using a computationalmeans to form a fitting operation to a binding site on the kallikrein 7.The three dimensional structure of kallikrein 7 as provided in thepresent invention by the structure coordinates of Table 3 or a selectedportion of it, can be used together with various docking programs.

The potential inhibitory or binding effect of a chemical entity onkallikrein 7 may be analyzed prior to its actual synthesis and testingby the use of computer-modeling techniques. If the theoretical structureof the given chemical entity suggests insufficient interaction andassociation between it and Kallikrein 7, the need for synthesis andtesting of the chemical entity is obviated. However, if computermodeling indicates a strong interaction, the molecule may then besynthesized and tested for its ability to bind to kallikrein 7. Thus,expensive and time-consuming synthesis of inoperative compounds may beavoided.

This “in silico” analysis may begin by visual inspection of, forexample, the binding pocket on a computer screen based on the structuralcoordinates of Table 3 in whole or in part. Selected fragments orchemical entities may then be positioned in a variety of orientations,or “docked,” within the binding pocket of kallikrein 7. Docking may beaccomplished using software such as Quanta and SYBYL, followed by energyminimization and molecular dynamics with standard molecular mechanicsforce fields, such as CHARMM and AMBER. Specialized computer programsmay be of use for selecting interesting fragments or chemical entities.These programs include, for example, GRID, available from OxfordUniversity, Oxford, UK; 5 MCSS or CATALYST, available from MolecularSimulations, Burlington, Mass.; AUTODOCK, available from ScrippsResearch Institute, La Jolla, Calif.; DOCK, available from University ofCalifornia, San Francisco, Calif., and XSITE, available from UniversityCollege of London, UK.

Preferred is a method for designing a kallikrein 7 inhibitor whichinteracts at the substrate binding site of kallikrein 7 or any otherbinding sites. One approach enabled by this invention is the use of thestructure coordinates of kallikrein 7 to design chemical entities thatbind to or associate with Kallikrein 7 and alter the physical propertiesof the chemical entities in different ways. Thus, properties such as,for example, solubility, affinity, specificity, potency, on/off rates,or other binding characteristics may all be altered and/or maximized.One may design desired chemical entities by probing a kallikrein 7comprising the binding pocket of the invention with a library ofdifferent entities to determine optimal sites for interaction betweencandidate chemical entities and kallikrein 7. For example,high-resolution X-ray diffraction data collected from crystals saturatedwith solvent allows the determination of where each type of solventmolecule adheres. Small molecules that bind tightly to those sites canthen be designed and synthesized and tested for the desired activity.Once the desired activity is obtained, the molecules can be furtheraltered to maximize desirable properties.

Once a compound has been designed or selected by the above methods, theefficiency with which that compound may bind to kallikrein 7 may betested and modified for the maximum desired characteristic(s) usingcomputational or experimental evaluation. Various parameters can bemaximized depending on the desired result. These include, but are notlimited to, specificity, affinity, on/off rates, hydrophobicity,solubility, and other characteristics readily identifiable by theskilled artisan.

In a preferred embodiment, the structure coordinates of Table 3 ofkallikrein 7 is used in the above computer-based design step.

The invention further relates to a method for selecting a ligand thatbinds to kallikrein 7, comprising:

a. co-crystallizing or incubating a candidate compound or mix ofcompounds with kallikrein 7 under appropriate conditions,b. determining by X-ray or NMR methods the amino acids of kallikrein 7which interacts with the candidate compound,c. selecting the compound which interacts at least with one or moreamino acids of the binding pocket.

For carrying out step b., mapping of the binding site of ligand isusually performed by recording NMR spectra with and without thecandidate compound, and identifying those resonances of the protein thatare affected by ligand binding. This requires assignment of the proteinresonance prior to the analysis, or comparison with the pattern ofchemical shift changes that occur upon binding of ligands with knownbinding sites. Alternatively, competition experiments using said ligandswith known binding sites can yield equivalent information.

The present invention further provides methods to design novel ligandsof kallikrein 7, using fragment linking approaches. Compounds binding todifferent binding regions of Kallikrein 7 are first selected. Theligands are linked together based on the spatial orientation, so thatthe designed novel compounds fits within the two binding sites.

The invention thus relates to a method to design ligands to kallikrein7, wherein said method comprises:

a. providing a first ligand that binds to one or more amino acids of afirst binding region of kallikrein 7,

b. providing a second ligand that binds to one or more amino acids of asecond binding region of Kallikrein 7, and,

c. linking said first ligand to said second ligand to design a ligandthat binds to the first and second binding pockets of kallikrein 7.

The selection of an appropriate linking group is made by maintaining thespatial orientation of the ligands to one another and to kallikrein 7based upon principles of bond angle and bond length information wellknown in the organic chemical art.

In addition, antagonists of kallikrein 7 can be used to treat patients,or for the manufacture of a medicament to treat, for inflammatory and/orhyperpoliferative and pruritic skin diseases such as keloids,hypertrophic scars, acne, atopic dermatitis, psoriasis, pustularpsoriasis, rosacea, Netherton's syndrome or other pruritic dermatosessuch as prurigo nodularis, unspecified itch of the elderly as well asother diseases with epithelial barrier dysfunction such as aged skin,inflammatory bowel disease and Crohn's disease, as well as pancreatitis,or of cancer, in particular ovarian cancer.

The following examples serve to illustrate the present invention butshould not be construed as a limitation thereof. The inventionparticularly relates to the specific embodiments described in theseexamples.

EXAMPLES Cloning

To prevent autocleavage of hK7, the autocleavage site at position Tyr180(numbering according to Swiss-Prot entry P49862) has been mutated to Argby site-directed mutagenesis according to the standard protocol usingpET24_His-Pro-EK-KLK7(aa37-253) as template (QuickChange site-directedmutagenesis kit; Stratagene; mutagenesis primer: 5′GACTGCACGAAGGTTCGCAAGGACTTACTGGAAAATTCCATGC). Cloning of vectorpET24_His-Pro-EK-KLK7(aa37-253) has been in a manner usual in the art.The final vector was namedpET24c-His-ProKLK7-Enterok-KLK7(aa37-253)_Y180R.

Expression and Purification

E. coli strain BL21(DE3) harboring the expression plasmid for pro-hK7was cultivated at 37 C in LB medium containing 34 μg/ml chloramphenicoland 30 μg/ml kanamycin. Induction was started with 0.4 mM IPTG at anOD₆₀₀ of 1.0 for 4 hours at 37° C. Subsequently, the cells wereharvested by centrifugation. All purification steps were done at 4 C,unless stated otherwise. Cells from 10 liter E. coli cell culture (25 gcell pellet) were resuspended in 200 ml 50 mM Tris/HCl buffer, pH 8.0containing 1 mM MgCl₂ and stored at −20° C. overnight. After thawing, 1μl Benzonase (ROCHE) was added and the sample was incubated for 10 minat 37° C. The cells were ruptured by sonication (4 times 20 seconds at70% amplitude; Branson Digital Sonifier W-450D) and the homogenate wascentrifuged at 7000 g for 15 min. The inclusion body-containing pelletwas washed three times with 50 mM Tris pH 8.0 buffer containing 25%sucrose, 1% Triton 100 and 1 μl Benzonase and finally two times with H₂Ocontaining 1 mM MgCl₂. The inclusion bodies were further purified byHPLC using a reverse phase column. For this, the inclusion bodies weredissolved in 6 M GuHCl (10 mg/ml) and 100 mM DTT and applied to a GESource RPC column (Fine line 35S) equilibrated with 0.1% TFA and 10%acetonitrile. The protein was eluted by an increasing acetonitrileconcentration from 10-100%. Fractions containing the protease werepooled and lyophilized. The dried protein was diluted to a finalconcentration of 50 μg/ml in 50 mM Tris/HCl pH 8.0 buffer (10° C. cold)containing 2 M urea, 500 mM NaCl, 10 mM CaCl₂, 0.1 M NH₄Cl, 1 mM EDTA,1.25 mM GSH and 0.5 mM GSSG. Subsequently, the sample was dialyzedagainst 10 mM Tris pH 8.0 buffer and loaded on a Q-sepharose column (50ml). The protein was eluted by an increasing salt concentration from0-0.5 M NaCl and fractions containing pro-hK7 were pooled andconcentrated to approx. 5 ml. Subsequently, the sample was activated bythe addition of enterokinase (1:100) for 24 h at 8° C. Finally, hK7 wasapplied to a size exclusion chromatography column (Superdex 75, HiLoad26/60, Amersham) equilibrated with 50 mM Tris, 100 mM NaCl, pH 8 at aflow rate of 2.5 ml/min. For crystallization trials the protein bufferwas exchanged by dialysis against 50 mM sodium acetate at pH 5.6 and 100mM sodium chloride and the protein was stored at 4° C.

Crystallization

hK7 was concentrated to 24.6 mg/ml and crystallized at 20° C. by thevapor diffusion method in hanging drops. 0.5 μl protein solutioncontaining 50 mM sodium acetate at pH 5.6, 100 mM sodium chloride, 2 mMinhibitor and 1.8% (v/v) DMSO was mixed with 0.5 μl reservoir solutioncomposed of 35% (w/v) PEG 3350, 200 mM calcium chloride and 100 mMsodium acetate at pH 4.8. The drops were equilibrated against 1 ml ofthe reservoir solution. Diffracting quality crystals appeared within 1-3days.

Data Collection

For X-ray data collection a crystal was flash frozen in liquid nitrogenwithout additional cryo-protectant. The X-ray diffraction data werecollected from a single crystal for the hK7-inhibitor complex at 95 K atthe beamline X10SA of the Swiss Light Source with a MAR225 mosaic CCDdetector at a wavelength of 0.9799 Å. For the crystals of hK7 in complexwith inhibitors, 299 or 300 images were collected, with 0.5° oscillationeach. The exposure time was between 0.5 s and 1 s per image. Thecrystal-to-detector distance was between 100 mm and 120 mm. The rawdiffraction data were processed and scaled with the HKL program suiteversion 1.98.0 (21) or with XDS/XSCALE (22) using the APRV (23)interface. The crystal data and data collection statistics aresummarized in Table 1.

TABLE 1 Data collection statistics Modulator Compound 1 X-ray sourceSLS/X10SA date of data collection 23.03.2006 Wavelength (Å) 0.979908Detector MARCCD 225 Temperature (K) 100 Number of crystals 1 Space groupP2₁2₁2₁ Unit cell dimensions: a, b, c (Å) 42.61, 60.34, 80.63 Number ofmonomers/a.u. 1 Packing coefficient (Å 3/Da) 2.1 Solvent content (%)41.5 Resolution range (Å) 33.5-1.1 Number of observations 312326 Numberof unique reflections 81660 Overall Data redundancy 3.8 Datacompleteness (%) 96.0% < 

 /σ (I)> 34.7 Rmerge 0.087 Highest resolution shell Resolution range1.14-1.10 Å Completeness for shell 73.9% < 

 /σ (I)> 2.2 Rmerge for shell 0.334 Rmerge = Σ|Io − <I>|/Σ<I>

Structure Determination and Structure Refinement

The hK7 structure in complex with compound 1 was solved by molecularreplacement with the program MOLREP version 9.2.10 (24), using thecoordinates of human kallikrein 1 (pdb code 1SPJ, refined to 1.7 Åresolution (25)) as a search model. With a high resolution data cut-offof 4.0 Å an unambiguous solution was found in space group P2₁2₁2₁ withone protein-modulator complex in the asymmetric unit (correlationcoefficient of 0.34, R-factor of 0.48). An initial refinement cycle wasapplied using the rigid-body, simulated-annealing and bindividualrefinement protocols of the program CNX version 2005 (26) and a highresolution data cut-off of 1.5 Å. The hK7 structure was build andrefined by alternating cycles of manual model (re)building using theprogram O version 9 (27) and automated refinement using the minimize andbindividual protocols of the program CNX version 2005. Subsequently, theresolution was extended to 1.2 Å, 209 water molecules were added usingthe water-pick protocol of the program CNX version 2005 and finally themodulator was added. Anisotropic displacement parameters were includedfor the final refinement cylces at 1.2 Å resolution using the adpprotocol of CNX 2005. The refinement target was the maximum likelihoodfunction with the parameters described by Engh and Huber (28) usingamplitudes. Cross validation was used throughout the refinement process,using 9.8% of the reflections which were excluded from the refinement.The quality of the final model was assessed with the programs CNX 2005and PROCHECK (29). The refinement statistics are summarized in Table 2.

TABLE 2 Refinement statistics Inhibitor Compound 1 Data used inrefinement resolution range 33.5-1.2 Å intensity cutoff (Sigma(F)) 0.0 number of reflections (working/test set) 58820/6415 completeness(working + test set) 89.5% test set  9.8% Fit to data used in refinementoverall Rcryst 0.181 overall Rfree 0.197 Fit in the highest resolutionbin resolution range 1.28-1.20 Å bin completeness (working + test set)99.5% bin Rcryst 0.182 bin Rfree 0.195 Number of non-hydrogen atomsprotein atoms 1785 inhibitor atoms  32 waters  209 Overall B value fromWilson plot 12.5 Å² Overall mean B value 16.4 Å² protein atoms 17.5 Å²inhibitor atoms 14.8 Å² water molecules 27.9 Å² Cross-validatedestimated coordinate error from Luzzati plot 0.13 Å from σA 0.01 Å Rmsdeviations from ideal values bond lengths 0.018 Å bond angles  1.7°dihedral angles 21.5° improper angles  1.3° Ramachandran plot residuesin most favorable regions 90.6% residues in additional allowed regions 9.4% Rcryst = Σ|Fo − Fc|/ΣFo

219 of the 224 amino acids could be traced in the high quality electrondensity map. Amino acids ¹⁶⁶RKDLL¹⁷⁰ (amino acid numbering according tothe chymotrypsinogen numbering scheme (30) is used throughout thedocument unless stated otherwise) lack electron density and were notincluded into the final structures. The arginine residue of thisdisordered loop is mutated in the construct used for crystallization(according to Swiss-Prot numbering entry P49862 this residue is Tyr180).The wild type tyrosine residue was prone to autocatalytic cleavage,which is not the case for the arginine mutant as was demonstrated by MSanalysis.

As expected, six disulfide bonds were found between residuesCys22-Cys157, Cys42-Cys58, Cys129-Cys232, Cys136-Cys201, Cys168-Cys182and Cys191-Cys220 and cis-peptide bonds were build for amino acidsPro147 and Pro219. Due to the high resolution of the structure the sidechains of amino acids 30, 38, 39, 49, 50, 84, 90, 110, 138, 153, 161,164, 187, 192 and 200 were build in two conformations

Structure of hK7

The structure of hK7 resembles the overall architecture of hK1, hK6 andhK8 (25, 31, 32) and follows the classical chymotrypsin like fold,composed of two β-barrels and a C-terminal α-helix. The active site,including the catalytic triad composed of His57, Asp102 and Ser195 islocated at the interface of the two 6-barrels.

Similar to hK5 and hK6 and in contrast to hK1, hK7 lacks the so calledkallikrein loop. The kallikrein loop is an insertion of up to 11 aminoacid residues between Thr96 and Gln97 characteristic for some of thekallikreins, especially the classical ones. It protrudes over thenon-primed binding site like a lid. hK7 has no amino acid insertion inthis region and is indistinguishable in length compared to trypsin orchymotrypsin.

Despite the overall structural similarity to other kallikreins, the S1pocket of hK7 differs from the trypsin-like specificity of e.g. hK1,hK5, hK6 and hK8 in that the polar Asn189 replaces the negativelycharged Asp at the bottom of the pocket and the hydrophobic Ala190substitutes the polar Ser/Thr residues. These specific structuralfeatures of the S1 pocket are well in agreement with the observedchymotrypsin-like specificity of hK7 with a preference for medium tolarge sized S1 residues with a polar tip. hK7 has a preferredspecificity for Tyr over Ala, Met and Phe in P1 (1, 33).

A disordered loop is located at the far end of the S3/S4 substratebinding pocket. In other S1 serine proteases complexed with inhibitorsbinding from S1 to S3, the homologous loop is ordered and folds backforming part of the S3/S4 binding pocket, thereby contributing toinhibitor binding. Therefore, it might be possible that this part of thekallikrein 7 structure gets ordered upon binding of inhibitors thatoccupy the S3/S4 pockets. In addition, due to the autocleavage after thetyrosine residue of this loop during purification, this tyrosine hasbeen replaced by an arginine residue, which might also influence theconformation of this loop.

Our modulators bind to the active site of kallikrein 7 adopting anunexpected binding mode spanning from S1 towards the primed bindingsite.

For compound 1 the naphthyl and methoxyphenyl moieties bind to the S1and S2′ pockets, respectively. The central pyrrolidine ring binds to theS1′ pocket and induces a conformational change of the His57 side chain,thereby disturbing the catalytic triad composed of His57, Asp102 andSer195. Upon inhibitor binding, the His57 side chain swings towards theS2 pocket (rotation around chi1 by 120° and around chi2 by 90° comparedto the structure of hK6 pdb code 1 L2E) and forms together with thedisulfide bond between Cys42 and Cys58 a hydrophobic pocket occupied bythe pyrrolidine ring of the inhibitor. The carbonyl oxygen atom of theinhibitor's urea moiety occupies the oxyanion hole and is in H-bondingdistance to the backbone nitrogen atoms of Gly193 and Ser195. One ureanitrogen atom makes water mediated interactions to the side chain ofHis57 and the backbone carbonyl group of Ser214. The inhibitor amidenitrogen atom interacts with the backbone carbonyl oxygen atom of His41.The methoxyphenyl moiety is in Van-der-Waals distance to Val149 andPhe151 with the phenyl ring making an edge-to-face interaction to theside chain of Phe151.

Within the crystal environment a symmetry related hK7 molecule packs inclose proximity to the active site of hK7. As previously mentioned, themodulator binding induces a movement of the catalytic His57 side chain.One nitrogen atom of this displaced His57 side chain is in H-bondingdistance to the backbone carbonyl group of Phe151 of the symmetryrelated molecule. In addition, the primed site moieties of themodulators are in contact with the side chains of Pro21 and Asp154 ofthe same symmetry related molecule. Therefore, an influence on thebinding modes of the modulators by the crystal contacts cannot betotally excluded. However, the crystal contact does not prevent bindingof different prime site scaffolds in different prime site pockets.

TABLE 3 Three-dimensional structure of the new binding pocket ofkallikrein 7 CRYST1 42.611 60.343 80.633 90.00 90.00 90.00 P 21 21 21 4ORIGX1 1.000000 0.000000 0.000000 0.00000 ORIGX2 0.000000 1.0000000.000000 0.00000 ORIGX3 0.000000 0.000000 1.000000 0.00000 SCALE10.023468 0.000000 0.000000 0.00000 SCALE2 0.000000 0.016572 0.0000000.00000 SCALE3 0.000000 0.000000 0.012402 0.00000 ATOM 1 CB ILE A  165.077 12.746 32.116 1.00 10.74 A C ANISOU 1 CB ILE A  16 1357 1177 13859 1 0 A C SIGUIJ 1 CB ILE A  16 22 18 18 999999 999999 999999 A C ATOM 2CG2 ILE A  16 4.414 12.703 30.717 1.00 11.43 A C ANISOU 2 CG2 ILE A  161373 1474 1390 7 −2 0 A C SIGUIJ 2 CG2 ILE A  16 22 13 13 999999 852999999 A C ATOM 3 CG1 ILE A  16 5.646 11.351 32.538 1.00 10.15 A CANISOU 3 CG1 ILE A  16 1298 1167 1395 −13 −4 0 A C SIGUIJ 3 CG1 ILE A 16 15 11 11 999999 999999 999999 A C ATOM 4 CD1 ILE A  16 6.590 10.68931.560 1.00 10.76 A C ANISOU 4 CD1 ILE A  16 1346 1238 1417 29 5 −1 A CSIGUIJ 4 CD1 ILE A  16 15 22 10 999999 999999 999999 A C ATOM 5 C ILE A 16 5.552 15.206 31.787 1.00 10.91 A C ANISOU 5 C ILE A  16 1183 10921440 4 −108 −3 A C SIGUIJ 5 C ILE A  16 12 15 9 999999 999999 999999 A CATOM 6 O ILE A  16 4.774 15.767 32.532 1.00 10.79 A O ANISOU 6 O ILE A 16 1286 1171 1507 63 −57 −6 A O SIGUIJ 6 O ILE A  16 1 0 0 221 57 289 AO ATOM 7 N ILE A  16 6.698 13.966 33.589 1.00 9.90 A N ANISOU 7 N ILE A 16 1283 1064 1282 59 0 1 A N SIGUIJ 7 N ILE A  16 1 0 0 221 66 290 A NATOM 8 CA ILE A  16 6.169 13.847 32.184 1.00 10.55 A C ANISOU 8 CA ILE A 16 1283 1114 1281 81 0 −1 A C SIGUIJ 8 CA ILE A  16 14 13 21 0 265989999999 A C ATOM 9 N ILE A  17 5.926 15.671 30.585 1.00 11.18 A N ANISOU9 N ILE A  17 1446 1153 1477 56 2 −2 A N SIGUIJ 9 N ILE A  17 1 0 0 22166 290 A N ATOM 10 CA ILE A  17 5.417 16.952 30.064 1.00 12.10 A CANISOU 10 CA ILE A  17 1450 1172 1618 57 −64 8 A C SIGUIJ 10 CA ILE A 17 8 9 12 156 1511 999999 A C ATOM 11 CB ILE A  17 6.529 17.735 29.3501.00 12.26 A C ANISOU 11 CB ILE A  17 1537 1234 1787 48 55 9 A C SIGUIJ11 CB ILE A  17 8 8 10 180 6 999999 A C ATOM 12 CG2 ILE A  17 5.94119.119 28.872 1.00 12.53 A C ANISOU 12 CG2 ILE A  17 1893 1304 1900 1892 15 A C SIGUIJ 12 CG2 ILE A  17 8 8 8 191 617 999999 A C ATOM 13 CG1ILE A  17 7.750 17.957 30.263 1.00 12.96 A C ANISOU 13 CG1 ILE A  171634 1643 1921 0 −58 −1 A C SIGUIJ 13 CG1 ILE A  17 8 7 7 197 676 999999A C ATOM 14 CD1 ILE A  17 7.426 18.712 31.538 1.00 13.60 A C ANISOU 14CD1 ILE A  17 1963 1656 1929 44 2 1 A C SIGUIJ 14 CD1 ILE A  17 8 7 6201 676 999999 A C ATOM 15 C ILE A  17 4.313 16.687 29.037 1.00 12.56 AC ANISOU 15 C ILE A  17 1402 1257 1586 32 −21 0 A C SIGUIJ 15 C ILE A 17 8 7 5 204 659 988023 A C ATOM 16 O ILE A  17 4.516 15.889 28.1221.00 12.36 A O ANISOU 16 O ILE A  17 1497 1275 1591 49 −5 1 A O SIGUIJ16 O ILE A  17 1 0 0 221 57 289 A O ATOM 17 N ASP A  18 3.150 17.34329.232 1.00 13.27 A N ANISOU 17 N ASP A  18 1416 1360 1685 89 −34 −3 A NSIGUIJ 17 N ASP A  18 1 0 0 221 66 290 A N ATOM 18 CA ASP A  18 2.00717.349 28.291 1.00 14.05 A C ANISOU 18 CA ASP A  18 1544 1613 1897 46−212 60 A C SIGUIJ 18 CA ASP A  18 7 7 4 206 638 855653 A C ATOM 19 CBASP A  18 2.386 17.918 26.913 1.00 15.58 A C ANISOU 19 CB ASP A  18 22631479 1926 68 −18 −3 A C SIGUIJ 19 CB ASP A  18 7 7 4 208 617 754615 A CATOM 20 CG ASP A  18 1.151 18.251 26.055 1.00 16.60 A C ANISOU 20 CG ASPA  18 2333 1838 1991 172 −63 −25 A C SIGUIJ 20 CG ASP A  18 7 7 3 209596 674948 A C ATOM 21 OD1 ASP A  18 0.112 18.577 26.628 1.00 18.23 A OANISOU 21 OD1 ASP A  18 2635 4119 2133 945 30 51 A O SIGUIJ 21 OD1 ASP A 18 1 0 0 221 57 289 A O ATOM 22 OD2 ASP A  18 1.233 18.185 24.829 1.0017.67 A O ANISOU 22 OD2 ASP A  18 2389 3156 1991 483 −53 −40 A O SIGUIJ22 OD2 ASP A  18 1 0 0 221 57 289 A O ATOM 23 C ASP A  18 1.403 15.96428.130 1.00 14.19 A C ANISOU 23 C ASP A  18 1588 1641 1795 −3 −25 −1 A CSIGUIJ 23 C ASP A  18 7 7 3 210 576 610513 A C ATOM 24 O ASP A  18 0.89515.606 27.045 1.00 14.18 A O ANISOU 24 O ASP A  18 1730 1957 1807 −162−32 −33 A O SIGUIJ 24 O ASP A  18 1 0 0 221 57 289 A O ATOM 25 N GLY A 19 1.416 15.209 29.232 1.00 14.20 A N ANISOU 25 N GLY A  19 1512 16121803 −41 −23 −6 A N SIGUIJ 25 N GLY A  19 1 0 0 221 66 290 A N ATOM 26CA GLY A  19 0.676 13.954 29.260 1.00 14.43 A C ANISOU 26 CA GLY A  191470 1590 2177 −13 −3 0 A C SIGUIJ 26 CA GLY A  19 7 7 2 16 2131 13262 AC ATOM 27 C GLY A  19 −0.615 14.053 30.048 1.00 14.46 A C ANISOU 27 CGLY A  19 1325 1580 1798 −38 −240 −26 A C SIGUIJ 27 C GLY A  19 7 8 2156 1509 13262 A C ATOM 28 O GLY A  19 −1.228 15.140 30.140 1.00 15.36 AO ANISOU 28 O GLY A  19 1457 1603 3368 13 40 −1 A O SIGUIJ 28 O GLY A 19 1 0 0 221 57 289 A O ATOM 29 N ALA A  20 −1.039 12.931 30.604 1.0014.61 A N ANISOU 29 N ALA A  20 1411 1582 1989 6 −73 2 A N SIGUIJ 29 NALA A  20 1 0 0 221 66 290 A N ATOM 30 CA ALA A  20 −2.330 12.843 31.2981.00 14.42 A C ANISOU 30 CA ALA A  20 1426 1559 2026 28 −54 5 A C SIGUIJ30 CA ALA A  20 7 8 2 180 1232 13262 A C ATOM 31 CB ALA A  20 −3.44412.549 30.291 1.00 15.24 A C ANISOU 31 CB ALA A  20 1603 2578 2199 −195−182 −43 A C SIGUIJ 31 CB ALA A  20 7 9 1 191 1068 13262 A C ATOM 32 CALA A  20 −2.215 11.693 32.256 1.00 14.43 A C ANISOU 32 C ALA A  20 12271549 1982 77 13 −2 A C SIGUIJ 32 C ALA A  20 6 9 1 197 955 13262 A CATOM 33 O ALA A  20 −1.402 10.791 32.055 1.00 13.98 A O ANISOU 33 O ALAA  20 1331 1642 1760 183 −31 14 A O SIGUIJ 33 O ALA A  20 1 0 0 221 57289 A O ATOM 34 N PRO A  21 −3.043 11.661 33.301 1.00 14.48 A N ANISOU34 N PRO A  21 1288 1632 2007 39 59 −5 A N SIGUIJ 34 N PRO A  21 1 0 0221 66 290 A N ATOM 35 CD PRO A  21 −4.048 12.644 33.756 1.00 14.83 A CANISOU 35 CD PRO A  21 1541 1800 2794 175 325 −92 A C SIGUIJ 35 CD PRO A 21 7 11 1 201 872 13263 A C ATOM 36 CA PRO A  21 −2.941 10.505 34.2191.00 14.80 A C ANISOU 36 CA PRO A  21 1375 1626 1987 3 4 0 A C SIGUIJ 36CA PRO A  21 7 13 1 204 807 13263 A C ATOM 37 CB PRO A  21 −4.067 10.76535.243 1.00 14.78 A C ANISOU 37 CB PRO A  21 1626 2137 2270 87 260 −36 AC SIGUIJ 37 CB PRO A  21 9 20 0 206 755 13263 A C ATOM 38 CG PRO A  21−4.249 12.306 35.208 1.00 15.02 A C ANISOU 38 CG PRO A  21 1710 21372810 95 340 −30 A C SIGUIJ 38 CG PRO A  21 5 0 0 208 712 13264 A C ATOM39 C PRO A  21 −3.124 9.168 33.462 1.00 15.07 A C ANISOU 39 C PRO A  211444 1620 1929 −40 41 6 A C SIGUIJ 39 C PRO A  21 5 1 1 209 675 13264 AC ATOM 40 O PRO A  21 −4.000 9.040 32.592 1.00 15.55 A O ANISOU 40 O PROA  21 1692 2259 2177 −91 −215 −34 A O SIGUIJ 40 O PRO A  21 1 0 0 221 57289 A O ATOM 41 N CYS A  22 −2.296 8.185 33.761 1.00 15.39 A N ANISOU 41N CYS A  22 1549 1659 2056 23 −11 1 A N SIGUIJ 41 N CYS A  22 1 0 0 22166 290 A N ATOM 42 CA CYS A  22 −2.418 6.865 33.130 1.00 15.88 A CANISOU 42 CA CYS A  22 1853 1653 2100 10 −75 −3 A C SIGUIJ 42 CA CYS A 22 5 1 1 210 644 13265 A C ATOM 43 C CYS A  22 −3.697 6.228 33.607 1.0016.58 A C ANISOU 43 C CYS A  22 1864 1719 2307 −16 −27 0 A C SIGUIJ 43 CCYS A  22 5 1 1 211 617 13265 A C ATOM 44 O CYS A  22 −4.105 6.44834.723 1.00 16.62 A O ANISOU 44 O CYS A  22 2051 1809 2331 −14 49 −2 A OSIGUIJ 44 O CYS A  22 1 0 0 221 57 289 A O ATOM 45 CB CYS A  22 −1.2595.925 33.523 1.00 15.41 A C ANISOU 45 CB CYS A  22 1802 1480 2278 −117−147 4 A C SIGUIJ 45 CB CYS A  22 5 1 1 212 592 13266 A C ATOM 46 SG CYSA  22 0.421 6.523 33.162 1.00 14.69 A S ANISOU 46 SG CYS A  22 1822 16961955 −194 −224 61 A S SIGUIJ 46 SG CYS A  22 1 0 0 221 49 289 A S ATOM47 N ALA A  23 −4.321 5.433 32.759 1.00 17.74 A N ANISOU 47 N ALA A  232277 1732 2634 5 −394 −34 A N SIGUIJ 47 N ALA A  23 1 0 0 221 66 290 A NATOM 48 CA ALA A  23 −5.508 4.669 33.194 1.00 18.55 A C ANISOU 48 CA ALAA  23 2391 1809 3463 −41 −135 −3 A C SIGUIJ 48 CA ALA A  23 5 1 1 213571 13267 A C ATOM 49 CB ALA A  23 −6.037 3.781 32.042 1.00 18.86 A CANISOU 49 CB ALA A  23 2965 2068 3487 −401 −128 −35 A C SIGUIJ 49 CB ALAA  23 5 1 1 213 552 13268 A C ATOM 50 C ALA A  23 −5.166 3.804 34.4071.00 19.23 A C ANISOU 50 C ALA A  23 1845 1832 3427 1 37 1 A C SIGUIJ 50C ALA A  23 5 1 1 214 534 13269 A C ATOM 51 O ALA A  23 −4.112 3.14434.461 1.00 18.85 A O ANISOU 51 O ALA A  23 1841 1831 3120 0 48 1 A OSIGUIJ 51 O ALA A  23 1 0 0 221 57 289 A O ATOM 52 N ARG A  24 −6.0323.816 35.411 1.00 20.08 A N ANISOU 52 N ARG A  24 1882 2804 3472 5 75 −1A N SIGUIJ 52 N ARG A  24 1 0 0 221 65 290 A N ATOM 53 CA ARG A  24−5.697 3.207 36.691 1.00 20.80 A C ANISOU 53 CA ARG A  24 1855 2815 3452129 140 −15 A C SIGUIJ 53 CA ARG A  24 5 1 1 214 518 13269 A C ATOM 54CB ARG A  24 −6.822 3.458 37.694 1.00 22.17 A C ANISOU 54 CB ARG A  243555 4746 5612 306 2004 −298 A C SIGUIJ 54 CB ARG A  24 5 1 1 214 50413270 A C ATOM 55 CG ARG A  24 −6.871 4.917 38.104 1.00 24.04 A C ANISOU55 CG ARG A  24 7566 4653 3991 894 390 104 A C SIGUIJ 55 CG ARG A  24 51 1 215 490 13271 A C ATOM 56 CD ARG A  24 −5.651 5.348 38.911 1.0025.58 A C ANISOU 56 CD ARG A  24 8395 7383 5215 −3 −385 2 A C SIGUIJ 56CD ARG A  24 5 1 1 215 478 13273 A C ATOM 57 NE ARG A  24 −6.074 5.58540.291 1.00 27.17 A N ANISOU 57 NE ARG A  24 10414 8862 5354 905 77 25 AN SIGUIJ 57 NE ARG A  24 1 0 0 221 65 290 A N ATOM 58 CZ ARG A  24−6.285 6.793 40.812 1.00 27.52 A C ANISOU 58 CZ ARG A  24 6679 8752 5430224 147 4 A C SIGUIJ 58 CZ ARG A  24 5 1 1 215 466 13274 A C ATOM 59 NH1ARG A  24 −6.098 7.887 40.064 1.00 28.32 A N ANISOU 59 NH1 ARG A  246831 8764 5428 172 118 4 A N SIGUIJ 59 NH1 ARG A  24 1 0 0 221 65 290 AN ATOM 60 NH2 ARG A  24 −6.731 6.923 42.060 1.00 28.06 A N ANISOU 60 NH2ARG A  24 5890 11495 5319 752 −191 −109 A N SIGUIJ 60 NH2 ARG A  24 1 00 221 65 290 A N ATOM 61 C ARG A  24 −5.476 1.724 36.489 1.00 20.46 A CANISOU 61 C ARG A  24 1964 2810 3539 158 110 −16 A C SIGUIJ 61 C ARG A 24 5 1 1 216 455 13275 A C ATOM 62 O ARG A  24 −6.252 1.056 35.774 1.0021.02 A O ANISOU 62 O ARG A  24 2562 3150 3998 −121 −294 −37 A O SIGUIJ62 O ARG A  24 1 0 0 221 57 289 A O ATOM 63 N GLY A  25 −4.405 1.18537.066 1.00 19.77 A N ANISOU 63 N GLY A  25 1694 2152 3266 −187 298 55 AN SIGUIJ 63 N GLY A  25 1 0 0 221 65 290 A N ATOM 64 CA GLY A  25 −4.142−0.252 36.960 1.00 19.02 A C ANISOU 64 CA GLY A  25 2494 2178 3788 −31221 −4 A C SIGUIJ 64 CA GLY A  25 5 1 1 216 445 13276 A C ATOM 65 C GLYA  25 −3.455 −0.704 35.691 1.00 18.44 A C ANISOU 65 C GLY A  25 15992043 3543 −102 −238 −3 A C SIGUIJ 65 C GLY A  25 5 1 1 216 436 13277 A CATOM 66 O GLY A  25 −3.197 −1.879 35.566 1.00 18.78 A O ANISOU 66 O GLYA  25 2182 2069 3909 1 −69 −1 A O SIGUIJ 66 O GLY A  25 1 0 0 221 57 289A O ATOM 67 N SER A  26 −3.101 0.199 34.775 1.00 17.58 A N ANISOU 67 NSER A  26 1637 1926 3293 −297 −416 −184 A N SIGUIJ 67 N SER A  26 1 0 0221 65 290 A N ATOM 68 CA SER A  26 −2.521 −0.204 33.539 1.00 16.76 A CANISOU 68 CA SER A  26 1639 1828 3224 −141 −487 −92 A C SIGUIJ 68 CA SERA  26 5 1 1 216 427 13279 A C ATOM 69 CB SER A  26 −2.959 0.744 32.4201.00 17.50 A C ANISOU 69 CB SER A  26 2341 1960 3304 23 −634 −58 A CSIGUIJ 69 CB SER A  26 5 1 1 216 419 13280 A C ATOM 70 OG SER A  26−2.523 2.081 32.633 1.00 17.84 A O ANISOU 70 OG SER A  26 2705 1973 2835−62 −851 69 A O SIGUIJ 70 OG SER A  26 1 0 0 221 57 289 A O ATOM 71 CSER A  26 −0.983 −0.267 33.562 1.00 15.79 A C ANISOU 71 C SER A  26 16421901 2649 −132 −475 −100 A C SIGUIJ 71 C SER A  26 4 1 1 216 411 13282 AC ATOM 72 O SER A  26 −0.388 −0.642 32.569 1.00 15.91 A O ANISOU 72 OSER A  26 1789 1923 2633 5 −449 −18 A O SIGUIJ 72 O SER A  26 1 0 0 22157 289 A O ATOM 73 N HIS A  27 −0.404 0.093 34.705 1.00 14.85 A N ANISOU73 N HIS A  27 1597 1233 2583 −97 −450 88 A N SIGUIJ 73 N HIS A  27 1 00 221 65 290 A N ATOM 74 CA HIS A  27 1.073 0.045 34.891 1.00 14.13 A CANISOU 74 CA HIS A  27 1596 1182 2242 −107 −396 104 A C SIGUIJ 74 CA HISA  27 4 1 1 217 404 13283 A C ATOM 75 CB HIS A  27 1.648 1.471 34.9611.00 14.38 A C ANISOU 75 CB HIS A  27 1622 1194 2354 −125 −156 −12 A CSIGUIJ 75 CB HIS A  27 4 1 1 217 397 13285 A C ATOM 76 CG HIS A  271.495 2.179 33.679 1.00 15.00 A C ANISOU 76 CG HIS A  27 1758 1278 2360−48 −128 −2 A C SIGUIJ 76 CG HIS A  27 4 1 1 217 390 13286 A C ATOM 77CD2 HIS A  27 2.337 2.364 32.656 1.00 15.85 A C ANISOU 77 CD2 HIS A  272142 1369 2619 15 183 34 A C SIGUIJ 77 CD2 HIS A  27 4 1 1 217 384 13288A C ATOM 78 ND1 HIS A  27 0.259 2.638 33.259 1.00 15.70 A N ANISOU 78ND1 HIS A  27 1802 1462 2672 0 −210 2 A N SIGUIJ 78 ND1 HIS A  27 1 0 0221 65 290 A N ATOM 79 CE1 HIS A  27 0.339 3.050 32.017 1.00 15.87 A CANISOU 79 CE1 HIS A  27 2573 1650 2706 234 −53 63 A C SIGUIJ 79 CE1 HISA  27 4 1 1 217 378 13290 A C ATOM 80 NE2 HIS A  27 1.584 2.889 31.6131.00 15.97 A N ANISOU 80 NE2 HIS A  27 2579 1630 2756 223 −27 16 A NSIGUIJ 80 NE2 HIS A  27 1 0 0 221 65 290 A N ATOM 81 C HIS A  27 1.499−0.711 36.103 1.00 13.41 A C ANISOU 81 C HIS A  27 1335 1030 2120 −38−247 −16 A C SIGUIJ 81 C HIS A  27 4 1 1 217 372 13292 A C ATOM 82 O HISA  27 2.230 −0.213 36.943 1.00 12.83 A O ANISOU 82 O HIS A  27 1319 12891972 −233 −109 9 A O SIGUIJ 82 O HIS A  27 1 0 0 221 57 289 A O ATOM 83N PRO A  28 1.059 −1.976 36.227 1.00 12.88 A N ANISOU 83 N PRO A  281587 1063 2237 −143 −402 36 A N SIGUIJ 83 N PRO A  28 1 0 0 221 65 290 AN ATOM 84 CD PRO A  28 0.178 −2.764 35.323 1.00 13.22 A C ANISOU 84 CDPRO A  28 1835 1215 2589 −167 −633 −88 A C SIGUIJ 84 CD PRO A  28 4 1 1217 366 13294 A C ATOM 85 CA PRO A  28 1.373 −2.734 37.452 1.00 12.51 AC ANISOU 85 CA PRO A  28 1385 1110 2197 −28 −278 24 A C SIGUIJ 85 CA PROA  28 4 1 1 217 361 13296 A C ATOM 86 CB PRO A  28 0.454 −3.952 37.3701.00 13.00 A C ANISOU 86 CB PRO A  28 1841 1359 2863 −369 −419 98 A CSIGUIJ 86 CB PRO A  28 4 1 1 218 356 13298 A C ATOM 87 CG PRO A  280.220 −4.146 35.990 1.00 13.60 A C ANISOU 87 CG PRO A  28 1975 1284 2883−96 −481 53 A C SIGUIJ 87 CG PRO A  28 4 1 1 218 351 13300 A C ATOM 88 CPRO A  28 2.842 −3.139 37.575 1.00 12.04 A C ANISOU 88 C PRO A  28 13771099 1824 −36 −239 19 A C SIGUIJ 88 C PRO A  28 4 1 1 218 347 13302 A CATOM 89 O PRO A  28 3.260 −3.581 38.616 1.00 11.68 A O ANISOU 89 O PRO A 28 1326 1114 1831 −80 −229 36 A O SIGUIJ 89 O PRO A  28 1 0 0 221 57289 A O ATOM 90 N TRP A  29 3.566 −2.991 36.501 1.00 11.90 A N ANISOU 90N TRP A  29 1528 1241 1911 −72 −107 −4 A N SIGUIJ 90 N TRP A  29 1 0 0221 65 290 A N ATOM 91 CA TRP A  29 4.996 −3.300 36.496 1.00 12.18 A CANISOU 91 CA TRP A  29 1523 1332 1800 −64 −101 15 A C SIGUIJ 91 CA TRP A 29 4 1 1 218 342 13304 A C ATOM 92 CB TRP A  29 5.462 −3.949 35.1701.00 13.13 A C ANISOU 92 CB TRP A  29 2014 1545 1850 145 −35 −22 A CSIGUIJ 92 CB TRP A  29 4 1 1 218 338 13306 A C ATOM 93 CG TRP A  294.557 −3.677 34.063 1.00 14.19 A C ANISOU 93 CG TRP A  29 1935 1421 184059 5 2 A C SIGUIJ 93 CG TRP A  29 4 1 1 218 334 13309 A C ATOM 94 CD2TRP A  29 4.456 −2.468 33.269 1.00 14.61 A C ANISOU 94 CD2 TRP A  291678 1431 1845 15 −7 0 A C SIGUIJ 94 CD2 TRP A  29 4 1 1 218 330 13311 AC ATOM 95 CE2 TRP A  29 3.367 −2.647 32.397 1.00 14.65 A C ANISOU 95 CE2TRP A  29 1668 2320 1813 −130 26 14 A C SIGUIJ 95 CE2 TRP A  29 4 1 1218 326 13313 A C ATOM 96 CE3 TRP A  29 5.164 −1.260 33.223 1.00 14.33 AC ANISOU 96 CE3 TRP A  29 1697 1435 1778 16 3 0 A C SIGUIJ 96 CE3 TRP A 29 4 1 1 218 322 13316 A C ATOM 97 CD1 TRP A  29 3.550 −4.500 33.6131.00 15.11 A C ANISOU 97 CD1 TRP A  29 2761 2440 1961 −856 −156 143 A CSIGUIJ 97 CD1 TRP A  29 4 1 1 218 319 13318 A C ATOM 98 NE1 TRP A  292.846 −3.888 32.651 1.00 15.86 A N ANISOU 98 NE1 TRP A  29 2881 25801940 −698 −148 114 A N SIGUIJ 98 NE1 TRP A  29 1 0 0 221 65 290 A N ATOM99 CZ2 TRP A  29 2.979 −1.691 31.498 1.00 15.40 A C ANISOU 99 CZ2 TRP A 29 2058 2335 1811 −28 17 0 A C SIGUIJ 99 CZ2 TRP A  29 4 1 1 218 31513321 A C ATOM 100 CZ3 TRP A  29 4.756 −0.305 32.310 1.00 14.89 A CANISOU 100 CZ3 TRP A  29 1979 1524 1775 179 30 17 A C SIGUIJ 100 CZ3 TRPA  29 4 1 1 218 312 13324 A C ATOM 101 CH2 TRP A  29 3.670 −0.537 31.4601.00 14.79 A C ANISOU 101 CH2 TRP A  29 2012 2299 1774 13 28 0 A CSIGUIJ 101 CH2 TRP A  29 4 1 1 218 308 13326 A C ATOM 102 C TRP A  295.828 −2.043 36.737 1.00 12.02 A C ANISOU 102 C TRP A  29 1359 1288 151812 23 1 A C SIGUIJ 102 C TRP A  29 3 1 1 218 305 13329 A C ATOM 103 OTRP A  29 7.069 −2.125 36.796 1.00 12.59 A O ANISOU 103 O TRP A  29 13551715 2100 60 1 0 A O SIGUIJ 103 O TRP A  29 1 0 0 221 57 289 A O ATOM104 N AGLN A  30 5.205 −0.863 36.830 0.50 11.35 A N ANISOU 104 N AGLN A 30 1329 1275 1273 −2 −1 0 A N SIGUIJ 104 N AGLN A  30 1 0 0 221 65 290A N ATOM 105 N BGLN A  30 5.203 −0.881 36.850 0.50 13.54 A N ANISOU 105N BGLN A  30 1323 1291 1407 0 0 0 A N SIGUIJ 105 N BGLN A  30 1 0 0 22165 290 A N ATOM 106 CA AGLN A  30 5.894 0.403 37.181 0.50 11.36 A CANISOU 106 CA AGLN A  30 1320 1267 1269 0 −2 0 A C SIGUIJ 106 CA AGLN A 30 3 1 1 218 302 13332 A C ATOM 107 CA BGLN A  30 5.970 0.313 37.1550.50 13.55 A C ANISOU 107 CA BGLN A  30 1312 1301 1399 0 −2 0 A C SIGUIJ107 CA BGLN A  30 3 1 1 218 299 13335 A C ATOM 108 CB AGLN A  30 5.0011.609 36.822 0.50 12.26 A C ANISOU 108 CB AGLN A  30 1333 1253 1305 −2 00 A C SIGUIJ 108 CB AGLN A  30 3 1 1 218 296 13338 A C ATOM 109 CB BGLNA  30 5.267 1.540 36.592 0.50 14.45 A C ANISOU 109 CB BGLN A  30 13351312 1452 0 −6 0 A C SIGUIJ 109 CB BGLN A  30 3 1 2 219 294 13341 A CATOM 110 CG AGLN A  30 5.508 3.025 37.334 0.50 14.52 A C ANISOU 110 CGAGLN A  30 1371 1241 1278 −7 1 0 A C SIGUIJ 110 CG AGLN A  30 3 1 2 219291 13344 A C ATOM 111 CG BGLN A  30 6.161 2.794 36.722 0.50 16.71 A CANISOU 111 CG BGLN A  30 1348 1315 1580 0 −35 0 A C SIGUIJ 111 CG BGLN A 30 3 1 2 219 288 13347 A C ATOM 112 CD AGLN A  30 6.288 3.795 36.2610.50 14.95 A C ANISOU 112 CD AGLN A  30 1351 1153 1282 37 5 2 A C SIGUIJ112 CD AGLN A  30 3 1 1 219 286 13350 A C ATOM 113 CD BGLN A  30 6.0133.746 35.560 0.50 17.14 A C ANISOU 113 CD BGLN A  30 2113 1379 1582 25576 29 A C SIGUIJ 113 CD BGLN A  30 3 1 1 35 2109 290 A C ATOM 114 OE1AGLN A  30 5.876 3.821 35.118 0.50 16.06 A O ANISOU 114 OE1 AGLN A  301451 2071 1288 196 −24 −17 A O SIGUIJ 114 OE1 AGLN A  30 1 0 0 221 57289 A O ATOM 115 OE1 BGLN A  30 5.231 3.488 34.662 0.50 18.25 A O ANISOU115 OE1 BGLN A  30 2203 1420 1669 292 −14 −6 A O SIGUIJ 115 OE1 BGLN A 30 1 0 0 221 57 289 A O ATOM 116 NE2 AGLN A  30 7.403 4.428 36.640 0.5016.36 A N ANISOU 116 NE2 AGLN A  30 1381 1242 1350 −6 0 0 A N SIGUIJ 116NE2 AGLN A  30 1 0 0 221 65 289 A N ATOM 117 NE2 BGLN A  30 6.748 4.85035.586 0.50 18.55 A N ANISOU 117 NE2 BGLN A  30 1820 1249 1612 450 53 57A N SIGUIJ 117 NE2 BGLN A  30 1 0 0 221 65 289 A N ATOM 118 C AGLN A  306.208 0.473 38.664 0.50 10.74 A C ANISOU 118 C AGLN A  30 1091 1125 1264−1 15 0 A C SIGUIJ 118 C AGLN A  30 3 1 1 157 1501 290 A C ATOM 119 CBGLN A  30 6.210 0.474 38.651 0.50 12.93 A C ANISOU 119 C BGLN A  301098 1088 1390 0 1 0 A C SIGUIJ 119 C BGLN A  30 3 1 1 181 1228 290 A CATOM 120 O AGLN A  30 5.337 0.147 39.489 0.50 10.87 A O ANISOU 120 OAGLN A  30 1106 1331 1279 −50 25 6 A O SIGUIJ 120 O AGLN A  30 1 0 0 22157 289 A O ATOM 121 O BGLN A  30 5.317 0.188 39.463 0.50 13.06 A OANISOU 121 O BGLN A  30 1169 1313 1472 −63 66 19 A O SIGUIJ 121 O BGLN A 30 1 0 0 221 57 289 A O ATOM 122 N VAL A  31 7.422 0.905 39.005 1.009.60 A N ANISOU 122 N VAL A  31 1089 1057 1213 5 14 1 A N SIGUIJ 122 NVAL A  31 1 0 0 221 65 289 A N ATOM 123 CA VAL A  31 7.763 1.199 40.3671.00 9.54 A C ANISOU 123 CA VAL A  31 1166 1082 1207 −8 1 0 A C SIGUIJ123 CA VAL A  31 3 1 1 191 1065 290 A C ATOM 124 CB VAL A  31 8.7540.156 40.963 1.00 9.53 A C ANISOU 124 CB VAL A  31 1198 1106 1235 11 −10 A C SIGUIJ 124 CB VAL A  31 3 1 1 197 953 290 A C ATOM 125 CG1 VAL A 31 8.192 −1.238 40.888 1.00 10.19 A C ANISOU 125 CG1 VAL A  31 14571140 1524 −82 −5 −3 A C SIGUIJ 125 CG1 VAL A  31 3 1 1 201 870 290 A CATOM 126 CG2 VAL A  31 10.134 0.266 40.296 1.00 9.91 A C ANISOU 126 CG2VAL A  31 1206 1164 1260 3 4 0 A C SIGUIJ 126 CG2 VAL A  31 3 1 1 204806 290 A C ATOM 127 C VAL A  31 8.337 2.615 40.423 1.00 9.25 A C ANISOU127 C VAL A  31 1145 1079 1094 12 1 0 A C SIGUIJ 127 C VAL A  31 3 1 1206 754 290 A C ATOM 128 O VAL A  31 8.676 3.230 39.417 1.00 9.42 A OANISOU 128 O VAL A  31 1235 1123 1098 8 18 1 A O SIGUIJ 128 O VAL A  311 0 0 221 57 289 A O ATOM 129 N ALA A  32 8.436 3.153 41.652 1.00 9.37 AN ANISOU 129 N ALA A  32 1272 1099 1098 −23 16 −2 A N SIGUIJ 129 N ALA A 32 1 0 0 221 65 289 A N ATOM 130 CA ALA A  32 9.210 4.366 41.898 1.009.78 A C ANISOU 130 CA ALA A  32 1249 1094 1197 −13 −1 0 A C SIGUIJ 130CA ALA A  32 3 1 0 208 711 290 A C ATOM 131 CB ALA A  32 8.351 5.46042.481 1.00 9.76 A C ANISOU 131 CB ALA A  32 1359 1149 1201 66 10 3 A CSIGUIJ 131 CB ALA A  32 3 1 0 209 675 290 A C ATOM 132 C ALA A  3210.330 4.050 42.873 1.00 10.12 A C ANISOU 132 C ALA A  32 1242 1129 1199−11 −1 0 A C SIGUIJ 132 C ALA A  32 3 1 0 210 643 290 A C ATOM 133 O ALAA  32 10.139 3.271 43.844 1.00 10.36 A O ANISOU 133 O ALA A  32 14561231 1233 −165 −69 41 A O SIGUIJ 133 O ALA A  32 1 0 0 221 57 289 A OATOM 134 N LEU A  33 11.476 4.682 42.664 1.00 10.54 A N ANISOU 134 N LEUA  33 1224 1112 1226 3 0 0 A N SIGUIJ 134 N LEU A  33 1 0 0 221 65 289 AN ATOM 135 CA LEU A  33 12.560 4.613 43.607 1.00 11.11 A C ANISOU 135 CALEU A  33 1222 1142 1244 7 −3 0 A C SIGUIJ 135 CA LEU A  33 3 1 0 211616 290 A C ATOM 136 CB LEU A  33 13.898 4.466 42.877 1.00 12.76 A CANISOU 136 CB LEU A  33 1307 1723 1534 78 145 −32 A C SIGUIJ 136 CB LEUA  33 3 1 0 212 592 290 A C ATOM 137 CG LEU A  33 14.013 3.133 42.0961.00 13.82 A C ANISOU 137 CG LEU A  33 2005 1782 1606 316 −131 −94 A CSIGUIJ 137 CG LEU A  33 3 1 0 213 570 290 A C ATOM 138 CD1 LEU A  3315.339 3.077 41.298 1.00 15.26 A C ANISOU 138 CD1 LEU A  33 2152 33101943 551 89 191 A C SIGUIJ 138 CD1 LEU A  33 3 1 0 213 551 290 A C ATOM139 CD2 LEU A  33 13.824 1.976 43.017 1.00 14.92 A C ANISOU 139 CD2 LEUA  33 3327 1868 1759 214 9 1 A C SIGUIJ 139 CD2 LEU A  33 3 1 0 214 534290 A C ATOM 140 C LEU A  33 12.540 5.910 44.392 1.00 11.52 A C ANISOU140 C LEU A  33 1208 1140 1249 −7 −1 0 A C SIGUIJ 140 C LEU A  33 3 1 0214 518 290 A C ATOM 141 O LEU A  33 12.664 7.004 43.780 1.00 10.87 A OANISOU 141 O LEU A  33 1395 1137 1241 −18 13 −1 A O SIGUIJ 141 O LEU A 33 1 0 0 221 57 289 A O ATOM 142 N LEU A  34 12.396 5.788 45.715 1.0011.68 A N ANISOU 142 N LEU A  34 1170 1376 1248 15 3 0 A N SIGUIJ 142 NLEU A  34 1 0 0 221 65 289 A N ATOM 143 CA LEU A  34 12.314 6.943 46.6041.00 12.60 A C ANISOU 143 CA LEU A  34 1479 1370 1243 7 73 3 A C SIGUIJ143 CA LEU A  34 3 1 0 214 503 290 A C ATOM 144 CB LEU A  34 11.0816.842 47.541 1.00 12.95 A C ANISOU 144 CB LEU A  34 1514 1734 1296 −17119 10 A C SIGUIJ 144 CB LEU A  34 3 1 0 215 490 290 A C ATOM 145 CG LEUA  34 9.777 6.385 46.830 1.00 12.96 A C ANISOU 145 CG LEU A  34 16071906 1508 −69 −3 1 A C SIGUIJ 145 CG LEU A  34 3 1 0 215 477 290 A CATOM 146 CD1 LEU A  34 8.650 6.238 47.872 1.00 13.74 A C ANISOU 146 CD1LEU A  34 1687 2206 1548 −130 51 −19 A C SIGUIJ 146 CD1 LEU A  34 3 1 0215 466 290 A C ATOM 147 CD2 LEU A  34 9.357 7.365 45.767 1.00 13.15 A CANISOU 147 CD2 LEU A  34 1786 1933 1514 11 −1 0 A C SIGUIJ 147 CD2 LEU A 34 3 1 0 216 455 290 A C ATOM 148 C LEU A  34 13.565 7.002 47.468 1.0013.57 A C ANISOU 148 C LEU A  34 1511 1624 1306 −12 30 1 A C SIGUIJ 148C LEU A  34 3 1 0 216 445 290 A C ATOM 149 O LEU A  34 14.159 5.98747.850 1.00 13.68 A O ANISOU 149 O LEU A  34 1564 1637 1416 2 −11 0 A OSIGUIJ 149 O LEU A  34 1 0 0 221 57 289 A O ATOM 150 N SER A  35 13.9368.232 47.793 1.00 14.73 A N ANISOU 150 N SER A  35 1898 1654 1350 −116−70 21 A N SIGUIJ 150 N SER A  35 1 0 0 221 65 289 A N ATOM 151 CA SER A 35 14.881 8.464 48.857 1.00 16.41 A C ANISOU 151 CA SER A  35 2180 24691578 −157 −305 −116 A C SIGUIJ 151 CA SER A  35 3 1 0 216 436 290 A CATOM 152 CB SER A  35 15.753 9.660 48.459 1.00 17.26 A C ANISOU 152 CBSER A  35 2216 2459 2653 −95 0 0 A C SIGUIJ 152 CB SER A  35 3 1 0 216427 290 A C ATOM 153 OG SER A  35 16.663 9.949 49.532 1.00 19.50 A OANISOU 153 OG SER A  35 2541 5015 2800 −738 −110 −149 A O SIGUIJ 153 OGSER A  35 1 0 0 221 57 289 A O ATOM 154 C SER A  35 14.032 8.785 50.0831.00 16.90 A C ANISOU 154 C SER A  35 2398 2366 1625 −6 −193 2 A CSIGUIJ 154 C SER A  35 3 1 0 216 419 290 A C ATOM 155 O SER A  35 13.5219.891 50.175 1.00 16.99 A O ANISOU 155 O SER A  35 2400 2365 1781 0 −161−2 A O SIGUIJ 155 O SER A  35 1 0 0 221 57 289 A O ATOM 156 N GLY A  3613.870 7.816 50.996 1.00 17.66 A N ANISOU 156 N GLY A  36 2457 2401 1660−24 −183 29 A N SIGUIJ 156 N GLY A  36 1 0 0 221 65 289 A N ATOM 157 CAGLY A  36 12.902 7.996 52.076 1.00 18.35 A C ANISOU 157 CA GLY A  362983 2300 2129 −149 320 −62 A C SIGUIJ 157 CA GLY A  36 3 1 0 217 411290 A C ATOM 158 C GLY A  36 11.499 8.004 51.475 1.00 18.74 A C ANISOU158 C GLY A  36 2927 2453 1870 −152 436 −76 A C SIGUIJ 158 C GLY A  36 31 0 217 404 290 A C ATOM 159 O GLY A  36 11.031 6.959 50.980 1.00 19.36A O ANISOU 159 O GLY A  36 3305 2782 2182 −526 835 −406 A O SIGUIJ 159 OGLY A  36 1 0 0 221 57 289 A O ATOM 160 N AASN A  38 10.841 9.156 51.4770.50 19.21 A N ANISOU 160 N AASN A  38 2998 2481 1260 −106 463 −60 A NSIGUIJ 160 N AASN A  38 1 0 0 221 65 289 A N ATOM 161 N BASN A  3810.837 9.161 51.484 0.50 21.40 A N ANISOU 161 N BASN A  38 2935 24511681 −163 415 −91 A N SIGUIJ 161 N BASN A  38 1 0 0 221 65 289 A N ATOM162 CA AASN A  38 9.525 9.292 50.867 0.50 19.45 A C ANISOU 162 CA AASN A 38 3071 2625 1630 −86 299 −37 A C SIGUIJ 162 CA AASN A  38 3 1 0 217397 290 A C ATOM 163 CA BASN A  38 9.584 9.336 50.746 0.50 21.64 A CANISOU 163 CA BASN A  38 3238 2455 2604 −245 −109 36 A C SIGUIJ 163 CABASN A  38 3 1 0 217 390 290 A C ATOM 164 CB AASN A  38 8.565 9.93151.867 0.50 21.32 A C ANISOU 164 CB AASN A  38 3969 3097 1906 520 779254 A C SIGUIJ 164 CB AASN A  38 3 1 0 217 384 290 A C ATOM 165 CB BASNA  38 8.446 9.760 51.678 0.50 23.51 A C ANISOU 165 CB BASN A  38 36003504 2904 159 143 64 A C SIGUIJ 165 CB BASN A  38 3 1 0 217 378 290 A CATOM 166 CG AASN A  38 9.047 11.305 52.305 0.50 22.29 A C ANISOU 166 CGAASN A  38 4334 3158 2340 437 629 163 A C SIGUIJ 166 CG AASN A  38 3 1 0217 372 290 A C ATOM 167 CG BASN A  38 7.797 8.601 52.331 0.50 24.48 A CANISOU 167 CG BASN A  38 3999 3561 3006 25 316 14 A C SIGUIJ 167 CG BASNA  38 3 1 0 217 366 290 A C ATOM 168 OD1 AASN A  38 9.518 11.483 53.4180.50 23.94 A O ANISOU 168 OD1 AASN A  38 13642 4902 4099 786 −3366 −264A O SIGUIJ 168 OD1 AASN A  38 1 0 0 221 57 289 A O ATOM 169 OD1 BASN A 38 7.643 8.557 53.549 0.50 26.13 A O ANISOU 169 OD1 BASN A  38 46517786 3014 −907 366 32 A O SIGUIJ 169 OD1 BASN A  38 1 0 0 221 57 289 A OATOM 170 ND2 AASN A  38 8.954 12.272 51.420 0.50 23.58 A N ANISOU 170ND2 AASN A  38 3506 2961 2202 −23 218 −6 A N SIGUIJ 170 ND2 AASN A  38 10 0 221 65 289 A N ATOM 171 ND2 BASN A  38 7.399 7.631 51.525 0.50 25.77A N ANISOU 171 ND2 BASN A  38 5305 3691 3182 −249 −8 1 A N SIGUIJ 171ND2 BASN A  38 1 0 0 221 65 289 A N ATOM 172 C AASN A  38 9.587 10.17149.609 0.50 18.94 A C ANISOU 172 C AASN A  38 2703 2575 1608 −86 266 −69A C SIGUIJ 172 C AASN A  38 3 1 0 217 361 290 A C ATOM 173 C BASN A  389.640 10.322 49.580 0.50 21.13 A C ANISOU 173 C BASN A  38 2703 23942572 −42 49 −10 A C SIGUIJ 173 C BASN A  38 3 1 0 218 356 290 A C ATOM174 O AASN A  38 8.557 10.475 49.008 0.50 19.09 A O ANISOU 174 O AASN A 38 2944 2973 2298 −1 −114 −3 A O SIGUIJ 174 O AASN A  38 1 0 0 221 57289 A O ATOM 175 O BASN A  38 8.597 10.687 49.032 0.50 21.28 A O ANISOU175 O BASN A  38 2746 2555 2688 7 −5 0 A O SIGUIJ 175 O BASN A  38 1 0 0221 57 289 A O ATOM 176 N AGLN A  39 10.789 10.602 49.221 0.50 17.84 A NANISOU 176 N AGLN A  39 2564 1698 1697 277 233 69 A N SIGUIJ 176 N AGLNA  39 1 0 0 221 65 289 A N ATOM 177 N BGLN A  39 10.842 10.756 49.1950.50 20.03 A N ANISOU 177 N BGLN A  39 2585 2227 1629 17 −247 −9 A NSIGUIJ 177 N BGLN A  39 1 0 0 221 65 289 A N ATOM 178 CA AGLN A  3910.911 11.552 48.118 0.50 16.87 A C ANISOU 178 CA AGLN A  39 2168 16421636 149 59 16 A C SIGUIJ 178 CA AGLN A  39 3 1 0 218 351 290 A C ATOM179 CA BGLN A  39 10.968 11.684 48.078 0.50 19.06 A C ANISOU 179 CA BGLNA  39 2140 2182 1656 365 −2 −1 A C SIGUIJ 179 CA BGLN A  39 3 1 0 218346 290 A C ATOM 180 CB AGLN A  39 12.010 12.556 48.439 0.50 18.21 A CANISOU 180 CB AGLN A  39 2485 2055 1554 −214 134 −43 A C SIGUIJ 180 CBAGLN A  39 3 1 0 218 342 290 A C ATOM 181 CB BGLN A  39 12.119 12.67948.323 0.50 20.40 A C ANISOU 181 CB BGLN A  39 2467 2609 1793 −4 −34 2 AC SIGUIJ 181 CB BGLN A  39 3 1 0 218 338 290 A C ATOM 182 CG AGLN A  3911.590 13.519 49.543 0.50 20.94 A C ANISOU 182 CG AGLN A  39 4813 22471558 498 400 67 A C SIGUIJ 182 CG AGLN A  39 3 1 0 218 334 290 A C ATOM183 CG BGLN A  39 12.162 13.856 47.333 0.50 23.13 A C ANISOU 183 CG BGLNA  39 6609 2671 1942 540 793 97 A C SIGUIJ 183 CG BGLN A  39 3 1 0 218330 290 A C ATOM 184 CD AGLN A  39 10.530 14.487 49.057 0.50 22.09 A CANISOU 184 CD AGLN A  39 4844 1804 3110 132 −396 −23 A C SIGUIJ 184 CDAGLN A  39 3 1 0 218 326 290 A C ATOM 185 CD BGLN A  39 13.249 14.88447.642 0.50 24.28 A C ANISOU 185 CD BGLN A  39 7887 3880 5011 −575 13 −2A C SIGUIJ 185 CD BGLN A  39 3 1 0 218 322 290 A C ATOM 186 OE1 AGLN A 39 10.757 15.244 48.122 0.50 23.85 A O ANISOU 186 OE1 AGLN A  39 79521817 3362 285 481 26 A O SIGUIJ 186 OE1 AGLN A  39 1 0 0 221 57 289 A OATOM 187 OE1 BGLN A  39 14.098 14.668 48.508 0.50 26.04 A O ANISOU 187OE1 BGLN A  39 9118 6539 6004 151 −1012 −51 A O SIGUIJ 187 OE1 BGLN A 39 1 0 0 221 57 289 A O ATOM 188 NE2 AGLN A  39 9.365 14.454 49.6820.50 23.39 A N ANISOU 188 NE2 AGLN A  39 5096 5212 3983 41 71 −10 A NSIGUIJ 188 NE2 AGLN A  39 1 0 0 221 65 289 A N ATOM 189 NE2 BGLN A  3913.221 16.010 46.939 0.50 25.58 A N ANISOU 189 NE2 BGLN A  39 6178 38514926 −526 159 −50 A N SIGUIJ 189 NE2 BGLN A  39 1 0 0 221 65 289 A NATOM 190 C AGLN A  39 11.215 10.869 46.777 0.50 15.25 A C ANISOU 190 CAGLN A  39 1586 1583 1636 0 0 0 A C SIGUIJ 190 C AGLN A  39 3 1 0 218318 290 A C ATOM 191 C BGLN A  39 11.231 10.914 46.773 0.50 17.44 A CANISOU 191 C BGLN A  39 1636 2081 1649 161 −1 3 A C SIGUIJ 191 C BGLN A 39 3 1 0 218 315 290 A C ATOM 192 O AGLN A  39 12.145 10.050 46.6760.50 14.48 A O ANISOU 192 O AGLN A  39 1594 1581 1457 0 −14 0 A O SIGUIJ192 O AGLN A  39 1 0 0 221 57 289 A O ATOM 193 O BGLN A  39 12.13810.069 46.696 0.50 16.67 A O ANISOU 193 O BGLN A  39 1674 2111 1542 191−4 −4 A O SIGUIJ 193 O BGLN A  39 1 0 0 221 57 289 A O ATOM 194 N LEU A 40 10.460 11.236 45.742 1.00 13.93 A N ANISOU 194 N LEU A  40 1491 15821598 −2 66 1 A N SIGUIJ 194 N LEU A  40 1 0 0 221 65 289 A N ATOM 195 CALEU A  40 10.683 10.606 44.410 1.00 12.92 A C ANISOU 195 CA LEU A  401356 1524 1597 −31 53 8 A C SIGUIJ 195 CA LEU A  40 3 1 0 218 312 290 AC ATOM 196 CB LEU A  40 9.769 11.223 43.394 1.00 12.72 A C ANISOU 196 CBLEU A  40 1493 1494 1694 −1 −55 −8 A C SIGUIJ 196 CB LEU A  40 3 1 0 218308 290 A C ATOM 197 CG LEU A  40 10.039 10.715 41.963 1.00 12.55 A CANISOU 197 CG LEU A  40 1722 1387 1706 −5 0 0 A C SIGUIJ 197 CG LEU A 40 3 1 0 218 305 290 A C ATOM 198 CD1 LEU A  40 9.679 9.246 41.850 1.0012.53 A C ANISOU 198 CD1 LEU A  40 1609 1377 1747 14 2 0 A C SIGUIJ 198CD1 LEU A  40 3 1 0 218 302 290 A C ATOM 199 CD2 LEU A  40 9.166 11.49740.989 1.00 12.87 A C ANISOU 199 CD2 LEU A  40 2090 1780 1721 377 −27−22 A C SIGUIJ 199 CD2 LEU A  40 3 1 0 218 299 290 A C ATOM 200 C LEU A 40 12.119 10.859 43.997 1.00 12.46 A C ANISOU 200 C LEU A  40 1335 11971424 25 5 0 A C SIGUIJ 200 C LEU A  40 3 1 0 218 296 290 A C ATOM 201 OLEU A  40 12.604 12.013 44.012 1.00 12.88 A O ANISOU 201 O LEU A  401625 1248 1672 −94 3 3 A O SIGUIJ 201 O LEU A  40 1 0 0 221 57 289 A OATOM 202 N HIS A  41 12.788 9.810 43.565 1.00 11.50 A N ANISOU 202 N HISA  41 1248 1160 1302 −24 1 0 A N SIGUIJ 202 N HIS A  41 1 0 0 221 65 289A N ATOM 203 CA HIS A  41 14.095 9.947 42.933 1.00 10.71 A C ANISOU 203CA HIS A  41 1249 1155 1274 −28 0 0 A C SIGUIJ 203 CA HIS A  41 3 1 0219 293 290 A C ATOM 204 CB HIS A  41 15.128 9.142 43.722 1.00 10.98 A CANISOU 204 CB HIS A  41 1266 1209 1307 −4 −1 0 A C SIGUIJ 204 CB HIS A 41 3 1 0 219 291 290 A C ATOM 205 CG HIS A  41 16.523 9.500 43.347 1.0010.96 A C ANISOU 205 CG HIS A  41 1281 1429 1279 −91 2 6 A C SIGUIJ 205CG HIS A  41 2 1 0 219 288 290 A C ATOM 206 CD2 HIS A  41 17.517 8.80042.755 1.00 10.94 A C ANISOU 206 CD2 HIS A  41 1306 1513 1249 −42 −1 0 AC SIGUIJ 206 CD2 HIS A  41 2 1 0 219 285 290 A C ATOM 207 ND1 HIS A  4117.048 10.749 43.618 1.00 11.76 A N ANISOU 207 ND1 HIS A  41 1482 14741696 −178 −65 −59 A N SIGUIJ 207 ND1 HIS A  41 1 0 0 221 65 289 A N ATOM208 CE1 HIS A  41 18.293 10.801 43.195 1.00 11.42 A C ANISOU 208 CE1 HISA  41 1480 1707 1745 −159 −40 −22 A C SIGUIJ 208 CE1 HIS A  41 2 1 0 219283 290 A C ATOM 209 NE2 HIS A  41 18.614 9.642 42.680 1.00 11.19 A NANISOU 209 NE2 HIS A  41 1406 1687 1633 −183 13 8 A N SIGUIJ 209 NE2 HISA  41 1 0 0 221 65 289 A N ATOM 210 C HIS A  41 14.067 9.523 41.444 1.0010.29 A C ANISOU 210 C HIS A  41 1182 1050 1269 −7 −3 0 A C SIGUIJ 210 CHIS A  41 2 1 0 219 280 290 A C ATOM 211 O HIS A  41 14.590 10.27340.588 1.00 10.52 A O ANISOU 211 O HIS A  41 1447 1068 1291 −92 77 −27 AO SIGUIJ 211 O HIS A  41 1 0 0 221 57 289 A O ATOM 212 N CYS A  4213.481 8.354 41.138 1.00 9.76 A N ANISOU 212 N CYS A  42 1233 1063 1149−34 10 −3 A N SIGUIJ 212 N CYS A  42 1 0 0 221 64 289 A N ATOM 213 CACYS A  42 13.458 7.885 39.760 1.00 9.65 A C ANISOU 213 CA CYS A  42 12221113 1149 −30 1 0 A C SIGUIJ 213 CA CYS A  42 2 1 0 219 278 290 A C ATOM214 C CYS A  42 12.287 6.932 39.567 1.00 9.15 A C ANISOU 214 C CYS A  421079 897 1150 151 1 −2 A C SIGUIJ 214 C CYS A  42 2 1 0 219 276 290 A CATOM 215 O CYS A  42 11.652 6.457 40.545 1.00 9.16 A O ANISOU 215 O CYSA  42 1210 1144 1141 −8 3 0 A O SIGUIJ 215 O CYS A  42 1 0 0 221 57 289A O ATOM 216 CB CYS A  42 14.705 7.106 39.423 1.00 10.11 A C ANISOU 216CB CYS A  42 1254 1211 1236 16 1 1 A C SIGUIJ 216 CB CYS A  42 2 1 0 219273 290 A C ATOM 217 SG CYS A  42 16.187 8.081 39.076 1.00 10.44 A SANISOU 217 SG CYS A  42 1259 1262 1221 0 5 0 A S SIGUIJ 217 SG CYS A  421 0 0 221 49 289 A S ATOM 218 N GLY A  43 11.981 6.644 38.326 1.00 9.41A N ANISOU 218 N GLY A  43 1123 916 1162 72 2 −2 A N SIGUIJ 218 N GLY A 43 1 0 0 221 64 289 A N ATOM 219 CA GLY A  43 11.122 5.525 38.028 1.009.14 A C ANISOU 219 CA GLY A  43 1184 946 1182 23 0 0 A C SIGUIJ 219 CAGLY A  43 2 1 0 219 271 290 A C ATOM 220 C GLY A  43 11.888 4.246 37.8481.00 9.24 A C ANISOU 220 C GLY A  43 1222 956 1143 35 7 2 A C SIGUIJ 220C GLY A  43 2 1 0 219 269 290 A C ATOM 221 O GLY A  43 13.118 4.21437.889 1.00 9.94 A O ANISOU 221 O GLY A  43 1219 1071 1587 27 5 0 A OSIGUIJ 221 O GLY A  43 1 0 0 221 56 289 A O ATOM 222 N GLY A  44 11.1543.165 37.568 1.00 9.21 A N ANISOU 222 N GLY A  44 1227 951 1241 46 0 0 AN SIGUIJ 222 N GLY A  44 1 0 0 221 64 289 A N ATOM 223 CA GLY A  4411.759 1.840 37.297 1.00 9.38 A C ANISOU 223 CA GLY A  44 1195 949 126942 −2 0 A C SIGUIJ 223 CA GLY A  44 2 1 0 219 267 290 A C ATOM 224 C GLYA  44 10.670 0.881 36.925 1.00 9.47 A C ANISOU 224 C GLY A  44 1167 9351090 60 8 4 A C SIGUIJ 224 C GLY A  44 2 1 0 219 265 290 A C ATOM 225 OGLY A  44 9.475 1.226 36.894 1.00 9.28 A O ANISOU 225 O GLY A  44 11541005 1272 64 11 −2 A O SIGUIJ 225 O GLY A  44 1 0 0 221 56 289 A O ATOM226 N VAL A  45 11.109 −0.343 36.641 1.00 9.57 A N ANISOU 226 N VAL A 45 1228 939 1165 63 9 5 A N SIGUIJ 226 N VAL A  45 1 0 0 221 64 289 A NATOM 227 CA VAL A  45 10.162 −1.428 36.379 1.00 10.47 A C ANISOU 227 CAVAL A  45 1349 1042 1480 −33 −43 −3 A C SIGUIJ 227 CA VAL A  45 2 1 0219 263 290 A C ATOM 228 CB VAL A  45 10.067 −1.867 34.895 1.00 11.25 AC ANISOU 228 CB VAL A  45 1934 1227 1484 57 −100 −12 A C SIGUIJ 228 CBVAL A  45 2 1 0 219 261 290 A C ATOM 229 CG1 VAL A  45 9.505 −0.69934.079 1.00 12.17 A C ANISOU 229 CG1 VAL A  45 2443 1284 1519 201 −199−37 A C SIGUIJ 229 CG1 VAL A  45 2 1 0 219 259 290 A C ATOM 230 CG2 VALA  45 11.426 −2.314 34.385 1.00 11.84 A C ANISOU 230 CG2 VAL A  45 19641327 1651 79 −23 −4 A C SIGUIJ 230 CG2 VAL A  45 2 1 0 219 257 290 A CATOM 231 C VAL A  45 10.536 −2.640 37.193 1.00 10.59 A C ANISOU 231 CVAL A  45 1193 1043 1477 −72 −27 1 A C SIGUIJ 231 C VAL A  45 2 1 0 219255 290 A C ATOM 232 O VAL A  45 11.695 −2.926 37.505 1.00 10.74 A OANISOU 232 O VAL A  45 1202 1061 1805 −105 −120 41 A O SIGUIJ 232 O VALA  45 1 0 0 221 56 289 A O ATOM 233 N LEU A  46 9.494 −3.408 37.539 1.0010.71 A N ANISOU 233 N LEU A  46 1168 973 1575 −10 4 0 A N SIGUIJ 233 NLEU A  46 1 0 0 221 64 289 A N ATOM 234 CA LEU A  46 9.719 −4.660 38.2561.00 10.83 A C ANISOU 234 CA LEU A  46 1417 991 1583 23 7 0 A C SIGUIJ234 CA LEU A  46 2 1 0 219 253 290 A C ATOM 235 CB LEU A  46 8.469−5.021 39.052 1.00 11.09 A C ANISOU 235 CB LEU A  46 1450 1269 1572 −646 1 A C SIGUIJ 235 CB LEU A  46 2 1 0 219 252 290 A C ATOM 236 CG LEU A 46 8.600 −6.228 39.986 1.00 11.03 A C ANISOU 236 CG LEU A  46 1562 12721562 −60 0 −2 A C SIGUIJ 236 CG LEU A  46 2 1 0 219 250 290 A C ATOM 237CD1 LEU A  46 9.556 −5.869 41.099 1.00 11.37 A C ANISOU 237 CD1 LEU A 46 1540 1181 1562 −1 0 0 A C SIGUIJ 237 CD1 LEU A  46 2 1 0 219 248 290A C ATOM 238 CD2 LEU A  46 7.237 −6.661 40.502 1.00 12.42 A C ANISOU 238CD2 LEU A  46 1663 1418 2039 −113 194 −12 A C SIGUIJ 238 CD2 LEU A  46 21 0 219 247 290 A C ATOM 239 C LEU A  46 10.037 −5.762 37.279 1.00 11.25A C ANISOU 239 C LEU A  46 1508 1024 1604 63 4 −1 A C SIGUIJ 239 C LEU A 46 2 1 0 219 245 290 A C ATOM 240 O LEU A  46 9.172 −6.116 36.443 1.0011.54 A O ANISOU 240 O LEU A  46 1554 1295 1635 −16 −8 −1 A O SIGUIJ 240O LEU A  46 1 0 0 221 56 289 A O ATOM 241 N VAL A  47 11.218 −6.36037.374 1.00 11.33 A N ANISOU 241 N VAL A  47 1473 917 1721 −1 −8 0 A NSIGUIJ 241 N VAL A  47 1 0 0 221 64 289 A N ATOM 242 CA VAL A  47 11.617−7.457 36.456 1.00 12.20 A C ANISOU 242 CA VAL A  47 1589 944 1749 22 80 A C SIGUIJ 242 CA VAL A  47 2 1 0 219 243 290 A C ATOM 243 CB VAL A 47 13.132 −7.531 36.319 1.00 11.95 A C ANISOU 243 CB VAL A  47 15881116 2027 27 27 −1 A C SIGUIJ 243 CB VAL A  47 2 1 0 219 242 290 A CATOM 244 CG1 VAL A  47 13.524 −8.722 35.459 1.00 12.53 A C ANISOU 244CG1 VAL A  47 1881 1165 2043 135 24 −11 A C SIGUIJ 244 CG1 VAL A  47 2 10 219 240 290 A C ATOM 245 CG2 VAL A  47 13.676 −6.210 35.700 1.00 12.70A C ANISOU 245 CG2 VAL A  47 1707 1139 2103 −9 56 3 A C SIGUIJ 245 CG2VAL A  47 2 1 0 219 239 290 A C ATOM 246 C VAL A  47 11.094 −8.79237.019 1.00 12.39 A C ANISOU 246 C VAL A  47 1511 945 1769 46 17 −1 A CSIGUIJ 246 C VAL A  47 2 1 0 219 237 290 A C ATOM 247 O VAL A  47 10.525−9.641 36.298 1.00 13.11 A O ANISOU 247 O VAL A  47 1875 1153 1846 −2009 −29 A O SIGUIJ 247 O VAL A  47 1 0 0 221 56 289 A O ATOM 248 N ASN A 48 11.274 −8.986 38.310 1.00 12.97 A N ANISOU 248 N ASN A  48 1610 10931767 10 −9 1 A N SIGUIJ 248 N ASN A  48 1 0 0 221 64 289 A N ATOM 249 CAASN A  48 10.692 −10.197 38.940 1.00 13.56 A C ANISOU 249 CA ASN A  481881 1184 1765 −143 −30 21 A C SIGUIJ 249 CA ASN A  48 2 1 0 219 236 290A C ATOM 250 CB ASN A  48 11.514 −11.465 38.691 1.00 13.95 A C ANISOU250 CB ASN A  48 1980 1232 1875 −85 −22 3 A C SIGUIJ 250 CB ASN A  48 21 0 219 234 290 A C ATOM 251 CG ASN A  48 12.949 −11.323 39.128 1.0014.48 A C ANISOU 251 CG ASN A  48 2032 1624 2353 −125 −178 8 A C SIGUIJ251 CG ASN A  48 2 1 0 219 233 290 A C ATOM 252 OD1 ASN A  48 13.236−10.802 40.234 1.00 14.80 A O ANISOU 252 OD1 ASN A  48 1744 1578 2355 13−166 −9 A O SIGUIJ 252 OD1 ASN A  48 1 0 0 221 56 289 A O ATOM 253 ND2ASN A  48 13.863 −11.736 38.267 1.00 15.49 A N ANISOU 253 ND2 ASN A  482331 2029 2614 46 56 −4 A N SIGUIJ 253 ND2 ASN A  48 1 0 0 221 64 289 AN ATOM 254 C ASN A  48 10.591 −9.863 40.432 1.00 14.01 A C ANISOU 254 CASN A  48 1938 1259 1777 −307 26 −25 A C SIGUIJ 254 C ASN A  48 2 1 0219 232 290 A C ATOM 255 O ASN A  48 10.777 −8.674 40.833 1.00 13.61 A OANISOU 255 O ASN A  48 1850 1230 1641 −252 −44 32 A O SIGUIJ 255 O ASN A 48 1 0 0 221 56 289 A O ATOM 256 N AGLU A  49 10.232 −10.835 41.2750.50 14.78 A N ANISOU 256 N AGLU A  49 1993 1342 1824 −383 −31 33 A NSIGUIJ 256 N AGLU A  49 1 0 0 221 64 289 A N ATOM 257 N BGLU A  4910.279 −10.868 41.259 0.50 16.97 A N ANISOU 257 N BGLU A  49 2692 14511833 −668 −125 73 A N SIGUIJ 257 N BGLU A  49 1 0 0 221 64 289 A N ATOM258 CA AGLU A  49 9.895 −10.519 42.670 0.50 15.14 A C ANISOU 258 CA AGLUA  49 1953 1282 1836 −526 −10 14 A C SIGUIJ 258 CA AGLU A  49 2 1 0 219230 290 A C ATOM 259 CA BGLU A  49 9.970 −10.660 42.680 0.50 17.33 A CANISOU 259 CA BGLU A  49 2140 2923 1801 −131 −322 −14 A C SIGUIJ 259 CABGLU A  49 2 1 0 219 229 290 A C ATOM 260 CB AGLU A  49 9.299 −11.75343.388 0.50 16.48 A C ANISOU 260 CB AGLU A  49 2320 1346 1820 −689 41−34 A C SIGUIJ 260 CB AGLU A  49 2 1 0 219 228 290 A C ATOM 261 CB BGLUA  49 9.618 −12.009 43.367 0.50 18.67 A C ANISOU 261 CB BGLU A  49 57352899 2972 33 1843 23 A C SIGUIJ 261 CB BGLU A  49 2 1 0 219 226 290 A CATOM 262 CG AGLU A  49 8.105 −12.394 42.692 0.50 18.70 A C ANISOU 262 CGAGLU A  49 2626 2154 1929 −1165 −48 54 A C SIGUIJ 262 CG AGLU A  49 2 10 219 225 290 A C ATOM 263 CG BGLU A  49 8.504 −12.838 42.715 0.50 20.89A C ANISOU 263 CG BGLU A  49 6858 2850 6466 104 −162 −36 A C SIGUIJ 263CG BGLU A  49 2 1 0 219 224 290 A C ATOM 264 CD AGLU A  49 8.468 −13.54441.739 0.50 19.66 A C ANISOU 264 CD AGLU A  49 3022 2158 1755 −883 −230149 A C SIGUIJ 264 CD AGLU A  49 2 1 0 219 223 290 A C ATOM 265 CD BGLUA  49 7.906 −13.862 43.655 0.50 21.85 A C ANISOU 265 CD BGLU A  49 62422697 6614 528 −98 69 A C SIGUIJ 265 CD BGLU A  49 2 1 0 219 222 290 A CATOM 266 OE1 AGLU A  49 9.352 −13.404 40.878 0.50 20.29 A O ANISOU 266OE1 AGLU A  49 3300 1254 2020 −905 54 −28 A O SIGUIJ 266 OE1 AGLU A  491 0 0 221 56 289 A O ATOM 267 OE1 BGLU A  49 8.685 −14.452 44.415 0.5022.48 A O ANISOU 267 OE1 BGLU A  49 5760 1973 6434 47 22 0 A O SIGUIJ267 OE1 BGLU A  49 1 0 0 221 56 289 A O ATOM 268 OE2 AGLU A  49 7.836−14.615 41.842 0.50 21.02 A O ANISOU 268 OE2 AGLU A  49 2538 1944 1986−562 −21 16 A O SIGUIJ 268 OE2 AGLU A  49 1 0 0 221 56 289 A O ATOM 269OE2 BGLU A  49 6.671 −14.055 43.646 0.50 23.21 A O ANISOU 269 OE2 BGLU A 49 6326 6186 4560 −14 −65 3 A O SIGUIJ 269 OE2 BGLU A  49 1 0 0 221 56289 A O ATOM 270 C AGLU A  49 11.092 −9.977 43.471 0.50 14.59 A C ANISOU270 C AGLU A  49 1877 959 1825 −364 −1 3 A C SIGUIJ 270 C AGLU A  49 2 10 219 220 290 A C ATOM 271 C BGLU A  49 11.117 −10.003 43.452 0.50 16.78A C ANISOU 271 C BGLU A  49 1898 2721 1417 −13 −68 2 A C SIGUIJ 271 CBGLU A  49 2 1 0 219 219 290 A C ATOM 272 O AGLU A  49 10.911 −9.40644.538 0.50 14.43 A O ANISOU 272 O AGLU A  49 1617 968 1833 −452 −2 −5 AO SIGUIJ 272 O AGLU A  49 1 0 0 221 56 289 A O ATOM 273 O BGLU A  4910.903 −9.403 44.497 0.50 16.62 A O ANISOU 273 O BGLU A  49 2607 27381454 3 81 −1 A O SIGUIJ 273 O BGLU A  49 1 0 0 221 56 289 A O ATOM 274 NAARG A  50 12.298 −10.150 42.935 0.50 14.49 A N ANISOU 274 N AARG A  501891 1588 1752 −249 −23 23 A N SIGUIJ 274 N AARG A  50 1 0 0 221 64 289A N ATOM 275 N BARG A  50 12.324 −10.137 42.917 0.50 16.68 A N ANISOU275 N BARG A  50 1933 1479 1657 −163 39 −17 A N SIGUIJ 275 N BARG A  501 0 0 221 64 289 A N ATOM 276 CA AARG A  50 13.500 −9.681 43.606 0.5014.49 A C ANISOU 276 CA AARG A  50 1818 1271 1701 −88 17 −7 A C SIGUIJ276 CA AARG A  50 2 1 0 219 218 290 A C ATOM 277 CA BARG A  50 13.521−9.691 43.604 0.50 16.68 A C ANISOU 277 CA BARG A  50 1925 1261 1694 −7821 −5 A C SIGUIJ 277 CA BARG A  50 2 1 0 219 217 290 A C ATOM 278 CBAARG A  50 14.485 −10.854 43.733 0.50 16.52 A C ANISOU 278 CB AARG A  502045 1410 2763 76 −144 −3 A C SIGUIJ 278 CB AARG A  50 2 1 0 219 216 290A C ATOM 279 CB BARG A  50 14.511 −10.863 43.682 0.50 18.71 A C ANISOU279 CB BARG A  50 2233 1459 2243 166 0 15 A C SIGUIJ 279 CB BARG A  50 21 0 220 215 290 A C ATOM 280 CG AARG A  50 14.078 −11.827 44.830 0.5019.27 A C ANISOU 280 CG AARG A  50 2668 1491 2900 48 68 56 A C SIGUIJ280 CG AARG A  50 2 1 0 220 214 290 A C ATOM 281 CG BARG A  50 15.776−10.563 44.436 0.50 21.46 A C ANISOU 281 CG BARG A  50 2299 2636 2258−105 5 −9 A C SIGUIJ 281 CG BARG A  50 2 1 0 220 213 290 A C ATOM 282 CDAARG A  50 14.453 −11.226 46.145 0.50 21.50 A C ANISOU 282 CD AARG A  504009 2861 2974 −1194 251 −214 A C SIGUIJ 282 CD AARG A  50 2 1 0 220 212290 A C ATOM 283 CD BARG A  50 15.496 −10.244 45.904 0.50 23.69 A CANISOU 283 CD BARG A  50 1961 2702 2258 −105 −36 −9 A C SIGUIJ 283 CDBARG A  50 2 1 0 220 210 290 A C ATOM 284 NE AARG A  50 14.330 −12.16347.243 0.50 23.77 A N ANISOU 284 NE AARG A  50 10900 2957 3100 −1335 899−149 A N SIGUIJ 284 NE AARG A  50 1 0 0 221 64 289 A N ATOM 285 NE BARGA  50 15.178 −11.468 46.633 0.50 25.96 A N ANISOU 285 NE BARG A  50 32682753 2278 −366 95 −42 A N SIGUIJ 285 NE BARG A  50 1 0 0 221 64 289 A NATOM 286 CZ AARG A  50 14.812 −11.933 48.455 0.50 24.33 A C ANISOU 286CZ AARG A  50 13002 3449 3369 −1870 159 −30 A C SIGUIJ 286 CZ AARG A  502 1 0 220 209 290 A C ATOM 287 CZ BARG A  50 14.845 −11.524 47.916 0.5026.52 A C ANISOU 287 CZ BARG A  50 6401 1896 2492 −303 909 −62 A CSIGUIJ 287 CZ BARG A  50 2 1 0 220 208 290 A C ATOM 288 NH1 AARG A  5015.452 −10.794 48.688 0.50 24.98 A N ANISOU 288 NH1 AARG A  50 7444 16725139 1342 −320 −124 A N SIGUIJ 288 NH1 AARG A  50 1 0 0 221 64 289 A NATOM 289 NH1 BARG A  50 14.778 −10.419 48.644 0.50 27.17 A N ANISOU 289NH1 BARG A  50 2982 1878 2323 88 −2 0 A N SIGUIJ 289 NH1 BARG A  50 1 00 221 64 289 A N ATOM 290 NH2 AARG A  50 14.635 −12.813 49.432 0.5025.28 A N ANISOU 290 NH2 AARG A  50 10903 3280 3376 −1231 350 −56 A NSIGUIJ 290 NH2 AARG A  50 1 0 0 221 64 289 A N ATOM 291 NH2 BARG A  5014.585 −12.699 48.471 0.50 27.47 A N ANISOU 291 NH2 BARG A  50 5043 19782193 −488 −128 21 A N SIGUIJ 291 NH2 BARG A  50 1 0 0 221 64 289 A NATOM 292 C AARG A  50 14.230 −8.472 42.996 0.50 13.60 A C ANISOU 292 CAARG A  50 1610 1207 1674 40 4 −1 A C SIGUIJ 292 C AARG A  50 2 1 0 220207 290 A C ATOM 293 C BARG A  50 14.234 −8.472 42.995 0.50 15.79 A CANISOU 293 C BARG A  50 1663 1187 1666 69 0 −8 A C SIGUIJ 293 C BARG A 50 2 1 0 220 207 290 A C ATOM 294 O AARG A  50 15.150 −7.938 43.6350.50 13.67 A O ANISOU 294 O AARG A  50 1658 1339 1681 −26 1 1 A O SIGUIJ294 O AARG A  50 1 0 0 221 56 289 A O ATOM 295 O BARG A  50 15.147−7.928 43.630 0.50 15.86 A O ANISOU 295 O BARG A  50 1742 1370 1670 −36−9 3 A O SIGUIJ 295 O BARG A  50 1 0 0 221 56 289 A O ATOM 296 N TRP A 51 13.850 −8.067 41.779 1.00 12.29 A N ANISOU 296 N TRP A  51 1505 11521666 −23 12 1 A N SIGUIJ 296 N TRP A  51 1 0 0 221 64 289 A N ATOM 297CA TRP A  51 14.687 −7.155 41.015 1.00 11.48 A C ANISOU 297 CA TRP A  511322 1088 1578 80 −57 4 A C SIGUIJ 297 CA TRP A  51 2 1 0 220 206 290 AC ATOM 298 CB TRP A  51 15.438 −7.960 39.942 1.00 11.69 A C ANISOU 298CB TRP A  51 1512 1196 1650 156 29 −17 A C SIGUIJ 298 CB TRP A  51 2 1 0220 205 290 A C ATOM 299 CG TRP A  51 16.522 −8.845 40.509 1.00 12.06 AC ANISOU 299 CG TRP A  51 1546 1244 1789 172 −23 4 A C SIGUIJ 299 CG TRPA  51 2 1 0 220 204 290 A C ATOM 300 CD2 TRP A  51 17.836 −8.423 40.8811.00 12.06 A C ANISOU 300 CD2 TRP A  51 1547 1134 2005 202 −63 2 A CSIGUIJ 300 CD2 TRP A  51 2 1 0 220 203 290 A C ATOM 301 CE2 TRP A  5118.523 −9.572 41.358 1.00 12.45 A C ANISOU 301 CE2 TRP A  51 1614 11232069 211 −80 5 A C SIGUIJ 301 CE2 TRP A  51 2 1 0 220 202 290 A C ATOM302 CE3 TRP A  51 18.514 −7.191 40.859 1.00 12.45 A C ANISOU 302 CE3 TRPA  51 1580 1160 2082 175 −53 −2 A C SIGUIJ 302 CE3 TRP A  51 2 1 0 220201 290 A C ATOM 303 CD1 TRP A  51 16.465 −10.197 40.765 1.00 12.45 A CANISOU 303 CD1 TRP A  51 1555 1255 2117 201 136 36 A C SIGUIJ 303 CD1TRP A  51 2 1 0 220 200 290 A C ATOM 304 NE1 TRP A  51 17.655 −10.61741.271 1.00 12.82 A N ANISOU 304 NE1 TRP A  51 1665 1140 2779 176 −14722 A N SIGUIJ 304 NE1 TRP A  51 1 0 0 221 64 289 A N ATOM 305 CZ2 TRP A 51 19.835 −9.530 41.785 1.00 12.49 A C ANISOU 305 CZ2 TRP A  51 16111163 2023 200 −56 7 A C SIGUIJ 305 CZ2 TRP A  51 2 1 0 220 199 290 A CATOM 306 CZ3 TRP A  51 19.811 −7.153 41.280 1.00 12.11 A C ANISOU 306CZ3 TRP A  51 1560 1152 1987 177 −12 1 A C SIGUIJ 306 CZ3 TRP A  51 2 10 220 198 290 A C ATOM 307 CH2 TRP A  51 20.475 −8.318 41.738 1.00 12.39A C ANISOU 307 CH2 TRP A  51 1622 1161 2100 192 −45 3 A C SIGUIJ 307 CH2TRP A  51 2 1 0 220 197 290 A C ATOM 308 C TRP A  51 13.891 −6.07240.335 1.00 10.92 A C ANISOU 308 C TRP A  51 1176 1024 1481 −8 7 0 A CSIGUIJ 308 C TRP A  51 2 1 0 220 197 290 A C ATOM 309 O TRP A  51 12.875−6.331 39.672 1.00 10.75 A O ANISOU 309 O TRP A  51 1253 1057 1624 −29−90 2 A O SIGUIJ 309 O TRP A  51 1 0 0 221 56 289 A O ATOM 310 N VAL A 52 14.461 −4.863 40.420 1.00 9.93 A N ANISOU 310 N VAL A  52 1180 10121381 3 5 0 A N SIGUIJ 310 N VAL A  52 1 0 0 221 64 289 A N ATOM 311 CAVAL A  52 13.946 −3.683 39.687 1.00 10.04 A C ANISOU 311 CA VAL A  521260 1029 1401 35 −8 1 A C SIGUIJ 311 CA VAL A  52 2 1 0 220 196 290 A CATOM 312 CB VAL A  52 13.646 −2.570 40.742 1.00 10.01 A C ANISOU 312 CBVAL A  52 1267 1028 1421 8 5 0 A C SIGUIJ 312 CB VAL A  52 2 1 0 220 195290 A C ATOM 313 CG1 VAL A  52 13.540 −1.174 40.086 1.00 10.49 A CANISOU 313 CG1 VAL A  52 1519 1027 1429 22 8 1 A C SIGUIJ 313 CG1 VAL A 52 2 1 0 220 194 290 A C ATOM 314 CG2 VAL A  52 12.358 −2.904 41.4421.00 10.41 A C ANISOU 314 CG2 VAL A  52 1315 1176 1577 −25 66 −2 A CSIGUIJ 314 CG2 VAL A  52 2 1 0 220 193 290 A C ATOM 315 C VAL A  5214.986 −3.249 38.695 1.00 9.93 A C ANISOU 315 C VAL A  52 1213 950 139598 −18 3 A C SIGUIJ 315 C VAL A  52 2 1 0 220 193 290 A C ATOM 316 O VALA  52 16.193 −3.210 39.022 1.00 10.38 A O ANISOU 316 O VAL A  52 12001474 1279 89 3 −2 A O SIGUIJ 316 O VAL A  52 1 0 0 221 56 289 A O ATOM317 N LEU A  53 14.537 −2.834 37.532 1.00 9.71 A N ANISOU 317 N LEU A 53 1220 933 1395 84 −2 0 A N SIGUIJ 317 N LEU A  53 1 0 0 221 64 289 AN ATOM 318 CA LEU A  53 15.414 −2.262 36.504 1.00 9.85 A C ANISOU 318 CALEU A  53 1255 969 1420 69 14 0 A C SIGUIJ 318 CA LEU A  53 2 1 0 220192 290 A C ATOM 319 CB LEU A  53 15.126 −2.913 35.149 1.00 10.62 A CANISOU 319 CB LEU A  53 1407 1063 1430 18 3 −3 A C SIGUIJ 319 CB LEU A 53 2 1 0 220 191 290 A C ATOM 320 CG LEU A  53 15.952 −2.426 33.9451.00 11.41 A C ANISOU 320 CG LEU A  53 1564 1285 1460 −109 58 −30 A CSIGUIJ 320 CG LEU A  53 2 1 0 220 190 290 A C ATOM 321 CD1 LEU A  5317.413 −2.811 34.144 1.00 11.99 A C ANISOU 321 CD1 LEU A  53 1598 17401791 0 14 0 A C SIGUIJ 321 CD1 LEU A  53 2 1 0 220 190 290 A C ATOM 322CD2 LEU A  53 15.368 −3.099 32.683 1.00 12.17 A C ANISOU 322 CD2 LEU A 53 1834 1300 1485 −176 −27 11 A C SIGUIJ 322 CD2 LEU A  53 2 1 0 220189 290 A C ATOM 323 C LEU A  53 15.139 −0.749 36.447 1.00 9.78 A CANISOU 323 C LEU A  53 1161 957 1161 42 0 0 A C SIGUIJ 323 C LEU A  53 21 0 220 188 290 A C ATOM 324 O LEU A  53 13.987 −0.283 36.434 1.00 9.80A O ANISOU 324 O LEU A  53 1161 1023 1414 59 −19 −2 A O SIGUIJ 324 O LEUA  53 1 0 0 221 56 289 A O ATOM 325 N THR A  54 16.206 0.054 36.393 1.009.36 A N ANISOU 325 N THR A  54 1186 980 1366 15 5 0 A N SIGUIJ 325 NTHR A  54 1 0 0 221 64 289 A N ATOM 326 CA THR A  54 16.127 1.504 36.3721.00 8.84 A C ANISOU 326 CA THR A  54 1075 983 1311 1 13 0 A C SIGUIJ326 CA THR A  54 2 1 0 220 187 290 A C ATOM 327 CB THR A  54 16.0052.003 37.822 1.00 9.07 A C ANISOU 327 CB THR A  54 1303 1023 1315 63 0 0A C SIGUIJ 327 CB THR A  54 2 1 0 220 187 290 A C ATOM 328 OG1 THR A  5415.735 3.395 37.800 1.00 9.46 A O ANISOU 328 OG1 THR A  54 1233 10211316 33 2 0 A O SIGUIJ 328 OG1 THR A  54 1 0 0 221 56 289 A O ATOM 329CG2 THR A  54 17.246 1.746 38.680 1.00 9.74 A C ANISOU 329 CG2 THR A  541317 1192 1327 102 0 2 A C SIGUIJ 329 CG2 THR A  54 2 1 0 220 186 290 AC ATOM 330 C THR A  54 17.386 2.042 35.672 1.00 8.45 A C ANISOU 330 CTHR A  54 1059 1008 1241 0 −14 0 A C SIGUIJ 330 C THR A  54 2 1 0 220185 290 A C ATOM 331 O THR A  54 18.135 1.279 35.019 1.00 8.67 A OANISOU 331 O THR A  54 1116 1041 1232 19 11 0 A O SIGUIJ 331 O THR A  541 0 0 221 56 289 A O ATOM 332 N ALA A  55 17.617 3.347 35.762 1.00 7.93A N ANISOU 332 N ALA A  55 1049 1005 1170 −2 −7 0 A N SIGUIJ 332 N ALA A 55 1 0 0 221 64 289 A N ATOM 333 CA ALA A  55 18.795 3.977 35.147 1.008.32 A C ANISOU 333 CA ALA A  55 1069 1011 1176 −7 12 0 A C SIGUIJ 333CA ALA A  55 2 1 0 220 185 290 A C ATOM 334 CB ALA A  55 18.411 5.40934.690 1.00 8.36 A C ANISOU 334 CB ALA A  55 1358 1036 1190 63 5 1 A CSIGUIJ 334 CB ALA A  55 2 1 0 220 184 290 A C ATOM 335 C ALA A  5519.957 4.000 36.103 1.00 8.62 A C ANISOU 335 C ALA A  55 1091 1008 1198−13 −14 0 A C SIGUIJ 335 C ALA A  55 2 0 0 220 183 290 A C ATOM 336 OALA A  55 19.779 4.158 37.313 1.00 9.17 A O ANISOU 336 O ALA A  55 12141103 1202 −8 0 0 A O SIGUIJ 336 O ALA A  55 1 0 0 221 56 289 A O ATOM337 N ALA A  56 21.161 3.886 35.553 1.00 8.88 A N ANISOU 337 N ALA A  561095 1072 1255 2 0 0 A N SIGUIJ 337 N ALA A  56 1 0 0 221 64 289 A NATOM 338 CA ALA A  56 22.391 4.022 36.349 1.00 9.13 A C ANISOU 338 CAALA A  56 1104 1100 1268 0 −8 0 A C SIGUIJ 338 CA ALA A  56 2 0 0 220183 290 A C ATOM 339 CB ALA A  56 23.610 3.713 35.508 1.00 9.18 A CANISOU 339 CB ALA A  56 1170 1355 1368 54 68 −18 A C SIGUIJ 339 CB ALA A 56 2 0 0 220 182 290 A C ATOM 340 C ALA A  56 22.554 5.400 37.029 1.009.29 A C ANISOU 340 C ALA A  56 1031 1098 1243 −5 28 1 A C SIGUIJ 340 CALA A  56 2 0 0 220 181 290 A C ATOM 341 O ALA A  56 23.143 5.504 38.1091.00 9.43 A O ANISOU 341 O ALA A  56 1154 1208 1275 1 −41 0 A O SIGUIJ341 O ALA A  56 1 0 0 221 56 289 A O ATOM 342 N HIS A  57 21.994 6.44036.418 1.00 9.29 A N ANISOU 342 N HIS A  57 957 1083 1231 −43 84 18 A NSIGUIJ 342 N HIS A  57 1 0 0 221 64 289 A N ATOM 343 CA HIS A  57 22.0407.794 36.980 1.00 9.88 A C ANISOU 343 CA HIS A  57 1219 1096 1260 −30 00 A C SIGUIJ 343 CA HIS A  57 2 0 0 220 181 290 A C ATOM 344 CB HIS A 57 21.411 8.781 35.963 1.00 10.96 A C ANISOU 344 CB HIS A  57 1419 12511271 138 58 39 A C SIGUIJ 344 CB HIS A  57 2 0 0 220 180 290 A C ATOM345 CG HIS A  57 21.862 10.199 36.174 1.00 12.51 A C ANISOU 345 CG HIS A 57 1737 1288 1898 38 −5 0 A C SIGUIJ 345 CG HIS A  57 2 0 0 220 179 290A C ATOM 346 CD2 HIS A  57 22.606 10.741 37.162 1.00 13.42 A C ANISOU346 CD2 HIS A  57 1862 1514 1884 −127 0 3 A C SIGUIJ 346 CD2 HIS A  57 20 0 220 179 290 A C ATOM 347 ND1 HIS A  57 21.560 11.229 35.324 1.0014.09 A N ANISOU 347 ND1 HIS A  57 2608 1322 1981 155 −147 −10 A NSIGUIJ 347 ND1 HIS A  57 1 0 0 221 64 289 A N ATOM 348 CE1 HIS A  5722.111 12.339 35.771 1.00 13.23 A C ANISOU 348 CE1 HIS A  57 2744 14801458 −159 453 −54 A C SIGUIJ 348 CE1 HIS A  57 2 0 0 220 178 290 A CATOM 349 NE2 HIS A  57 22.758 12.076 36.880 1.00 14.35 A N ANISOU 349NE2 HIS A  57 3163 1518 1641 −219 192 −26 A N SIGUIJ 349 NE2 HIS A  57 10 0 221 64 289 A N ATOM 350 C HIS A  57 21.270 7.859 38.294 1.00 9.53 AC ANISOU 350 C HIS A  57 1189 1089 1252 −5 1 0 A C SIGUIJ 350 C HIS A 57 2 0 0 220 177 290 A C ATOM 351 O HIS A  57 21.458 8.814 39.087 1.0010.26 A O ANISOU 351 O HIS A  57 1338 1104 1272 −37 1 0 A O SIGUIJ 351 OHIS A  57 1 0 0 221 56 289 A O ATOM 352 N CYS A  58 20.425 6.851 38.5541.00 9.49 A N ANISOU 352 N CYS A  58 1141 1056 1135 30 0 0 A N SIGUIJ352 N CYS A  58 1 0 0 221 64 289 A N ATOM 353 CA CYS A  58 19.571 6.82739.746 1.00 9.52 A C ANISOU 353 CA CYS A  58 1135 1174 1134 1 0 0 A CSIGUIJ 353 CA CYS A  58 2 0 0 220 177 290 A C ATOM 354 C CYS A  5820.272 6.262 40.960 1.00 9.45 A C ANISOU 354 C CYS A  58 1145 1141 11480 0 0 A C SIGUIJ 354 C CYS A  58 2 0 0 220 176 290 A C ATOM 355 O CYS A 58 19.644 6.126 42.034 1.00 9.93 A O ANISOU 355 O CYS A  58 1175 13461160 −85 0 −2 A O SIGUIJ 355 O CYS A  58 1 0 0 221 56 289 A O ATOM 356CB CYS A  58 18.255 6.019 39.504 1.00 9.74 A C ANISOU 356 CB CYS A  581142 1223 1171 −10 −1 0 A C SIGUIJ 356 CB CYS A  58 2 0 0 220 176 290 AC ATOM 357 SG CYS A  58 17.343 6.738 38.109 1.00 10.15 A S ANISOU 357 SGCYS A  58 1255 1365 1167 73 −21 −8 A S SIGUIJ 357 SG CYS A  58 1 0 0 22149 289 A S ATOM 358 N LYS A  59 21.545 5.879 40.830 1.00 9.63 A N ANISOU358 N LYS A  59 1153 1158 1143 0 0 0 A N SIGUIJ 358 N LYS A  59 1 0 0221 64 289 A N ATOM 359 CA LYS A  59 22.295 5.248 41.932 1.00 10.30 A CANISOU 359 CA LYS A  59 1207 1213 1158 0 −5 0 A C SIGUIJ 359 CA LYS A 59 2 0 0 220 175 290 A C ATOM 360 CB LYS A  59 23.780 5.188 41.566 1.0010.96 A C ANISOU 360 CB LYS A  59 1230 1351 1404 13 59 −5 A C SIGUIJ 360CB LYS A  59 2 0 0 220 174 290 A C ATOM 361 CG LYS A  59 24.660 4.44042.551 1.00 11.83 A C ANISOU 361 CG LYS A  59 1373 1413 1556 26 −75 22 AC SIGUIJ 361 CG LYS A  59 2 0 0 220 174 290 A C ATOM 362 CD LYS A  5924.533 2.938 42.481 1.00 12.32 A C ANISOU 362 CD LYS A  59 1496 14161989 5 −20 0 A C SIGUIJ 362 CD LYS A  59 2 0 0 220 173 290 A C ATOM 363CE LYS A  59 25.438 2.259 43.495 1.00 13.78 A C ANISOU 363 CE LYS A  591943 1448 2351 32 −400 22 A C SIGUIJ 363 CE LYS A  59 2 0 0 220 173 290A C ATOM 364 NZ LYS A  59 25.395 0.771 43.306 1.00 14.23 A N ANISOU 364NZ LYS A  59 1869 1446 2495 2 −88 −1 A N SIGUIJ 364 NZ LYS A  59 1 0 0221 64 289 A N ATOM 365 C LYS A  59 22.162 5.994 43.235 1.00 10.26 A CANISOU 365 C LYS A  59 1250 1239 1163 0 −3 0 A C SIGUIJ 365 C LYS A  592 0 0 220 172 290 A C ATOM 366 O LYS A  59 22.388 7.236 43.300 1.0010.37 A O ANISOU 366 O LYS A  59 1272 1239 1294 −6 0 0 A O SIGUIJ 366 OLYS A  59 1 0 0 221 56 289 A O ATOM 367 N MET A  60 21.881 5.232 44.2861.00 10.70 A N ANISOU 367 N MET A  60 1336 1275 1175 −9 −15 2 A N SIGUIJ367 N MET A  60 1 0 0 221 64 289 A N ATOM 368 CA MET A  60 21.897 5.74545.657 1.00 11.34 A C ANISOU 368 CA MET A  60 1248 1409 1190 −70 5 −4 AC SIGUIJ 368 CA MET A  60 2 0 0 220 172 290 A C ATOM 369 CB MET A  6020.485 6.153 46.160 1.00 11.40 A C ANISOU 369 CB MET A  60 1260 15081141 −54 5 −1 A C SIGUIJ 369 CB MET A  60 2 0 0 220 171 290 A C ATOM 370CG MET A  60 19.864 7.316 45.370 1.00 11.47 A C ANISOU 370 CG MET A  601539 1552 1210 0 −88 1 A C SIGUIJ 370 CG MET A  60 2 0 0 220 170 290 A CATOM 371 SD MET A  60 18.429 8.017 46.154 1.00 12.13 A S ANISOU 371 SDMET A  60 1617 1619 1416 0 32 −4 A S SIGUIJ 371 SD MET A  60 1 0 0 22149 289 A S ATOM 372 CE MET A  60 17.335 6.674 45.953 1.00 12.68 A CANISOU 372 CE MET A  60 1631 1618 1685 0 −1 0 A C SIGUIJ 372 CE MET A 60 2 0 0 220 170 290 A C ATOM 373 C MET A  60 22.473 4.642 46.538 1.0011.97 A C ANISOU 373 C MET A  60 1349 1454 1244 −22 −15 1 A C SIGUIJ 373C MET A  60 2 0 0 220 169 290 A C ATOM 374 O MET A  60 22.558 3.46846.135 1.00 11.95 A O ANISOU 374 O MET A  60 1622 1458 1361 6 −42 −1 A OSIGUIJ 374 O MET A  60 1 0 0 221 56 289 A O ATOM 375 N ASN A  61 22.8455.046 47.770 1.00 12.35 A N ANISOU 375 N ASN A  61 1484 1681 1245 −258 9−7 A N SIGUIJ 375 N ASN A  61 1 0 0 221 64 289 A N ATOM 376 CA ASN A  6123.360 4.027 48.734 1.00 13.41 A C ANISOU 376 CA ASN A  61 1617 17711319 −213 −53 15 A C SIGUIJ 376 CA ASN A  61 2 0 0 220 169 290 A C ATOM377 CB ASN A  61 23.892 4.694 50.038 1.00 14.86 A C ANISOU 377 CB ASN A 61 3266 1779 1457 −502 −580 159 A C SIGUIJ 377 CB ASN A  61 2 0 0 220168 290 A C ATOM 378 CG ASN A  61 22.813 5.445 50.823 1.00 16.38 A CANISOU 378 CG ASN A  61 3335 1441 1982 −792 −221 101 A C SIGUIJ 378 CGASN A  61 2 0 0 220 168 290 A C ATOM 379 OD1 ASN A  61 22.045 6.21350.270 1.00 18.80 A O ANISOU 379 OD1 ASN A  61 4072 2068 1933 −106 −27214 A O SIGUIJ 379 OD1 ASN A  61 1 0 0 221 56 289 A O ATOM 380 ND2 ASN A 61 22.736 5.213 52.150 1.00 16.96 A N ANISOU 380 ND2 ASN A  61 35633835 2029 −1706 −396 422 A N SIGUIJ 380 ND2 ASN A  61 1 0 0 221 64 289 AN ATOM 381 C ASN A  61 22.285 3.003 49.077 1.00 13.01 A C ANISOU 381 CASN A  61 1424 1571 1372 −3 −7 0 A C SIGUIJ 381 C ASN A  61 2 0 0 220167 290 A C ATOM 382 O ASN A  61 22.608 1.872 49.349 1.00 13.50 A OANISOU 382 O ASN A  61 1675 1609 1932 9 −255 91 A O SIGUIJ 382 O ASN A 61 1 0 0 221 56 289 A O ATOM 383 N GLU A  63 21.023 3.431 49.090 1.0012.53 A N ANISOU 383 N GLU A  63 1385 1471 1537 −62 −3 −1 A N SIGUIJ 383N GLU A  63 1 0 0 221 63 289 A N ATOM 384 CA GLU A  63 19.913 2.51349.306 1.00 12.71 A C ANISOU 384 CA GLU A  63 1326 1471 1544 −29 −20 −3A C SIGUIJ 384 CA GLU A  63 2 0 0 220 167 290 A C ATOM 385 CB GLU A  6319.736 2.165 50.795 1.00 14.43 A C ANISOU 385 CB GLU A  63 2200 17091562 −81 64 −8 A C SIGUIJ 385 CB GLU A  63 2 0 0 220 166 290 A C ATOM386 CG GLU A  63 19.298 3.358 51.617 1.00 16.54 A C ANISOU 386 CG GLU A 63 2343 1765 1556 27 −22 −1 A C SIGUIJ 386 CG GLU A  63 2 0 0 220 166290 A C ATOM 387 CD GLU A  63 19.201 3.109 53.132 1.00 18.20 A C ANISOU387 CD GLU A  63 2750 3194 1587 −794 −150 148 A C SIGUIJ 387 CD GLU A 63 2 0 0 220 165 290 A C ATOM 388 OE1 GLU A  63 19.523 1.977 53.5671.00 19.99 A O ANISOU 388 OE1 GLU A  63 4498 3286 1741 −416 −449 110 A OSIGUIJ 388 OE1 GLU A  63 1 0 0 221 56 289 A O ATOM 389 OE2 GLU A  6318.818 4.060 53.865 1.00 19.97 A O ANISOU 389 OE2 GLU A  63 4058 35631631 −98 −368 37 A O SIGUIJ 389 OE2 GLU A  63 1 0 0 221 56 289 A O ATOM390 C GLU A  63 18.664 3.191 48.763 1.00 12.29 A C ANISOU 390 C GLU A 63 1309 1487 1482 −25 −4 −1 A C SIGUIJ 390 C GLU A  63 2 0 0 220 165290 A C ATOM 391 O GLU A  63 18.691 4.408 48.431 1.00 11.91 A O ANISOU391 O GLU A  63 1594 1484 1449 −48 −8 3 A O SIGUIJ 391 O GLU A  63 1 0 0221 56 289 A O ATOM 392 N TYR A  64 17.566 2.423 48.707 1.00 11.40 A NANISOU 392 N TYR A  64 1302 1504 1269 −33 0 0 A N SIGUIJ 392 N TYR A  641 0 0 221 63 289 A N ATOM 393 CA TYR A  64 16.342 2.920 48.090 1.0011.01 A C ANISOU 393 CA TYR A  64 1304 1529 1246 −17 2 0 A C SIGUIJ 393CA TYR A  64 2 0 0 220 164 290 A C ATOM 394 CB TYR A  64 16.171 2.36946.649 1.00 11.12 A C ANISOU 394 CB TYR A  64 1399 1577 1236 −31 12 0 AC SIGUIJ 394 CB TYR A  64 2 0 0 220 164 290 A C ATOM 395 CG TYR A  6417.429 2.395 45.795 1.00 10.88 A C ANISOU 395 CG TYR A  64 1406 12991206 −27 9 −2 A C SIGUIJ 395 CG TYR A  64 2 0 0 220 163 290 A C ATOM 396CD1 TYR A  64 17.623 3.388 44.817 1.00 10.36 A C ANISOU 396 CD1 TYR A 64 1236 1307 1181 −10 −2 0 A C SIGUIJ 396 CD1 TYR A  64 2 0 0 220 163290 A C ATOM 397 CE1 TYR A  64 18.785 3.425 44.042 1.00 11.12 A C ANISOU397 CE1 TYR A  64 1251 1400 1198 −52 3 −1 A C SIGUIJ 397 CE1 TYR A  64 20 0 220 162 290 A C ATOM 398 CD2 TYR A  64 18.418 1.456 45.983 1.0010.39 A C ANISOU 398 CD2 TYR A  64 1401 1279 1269 −37 18 −5 A C SIGUIJ398 CD2 TYR A  64 2 0 0 220 162 290 A C ATOM 399 CE2 TYR A  64 19.5721.461 45.226 1.00 11.07 A C ANISOU 399 CE2 TYR A  64 1382 1442 1213 −5−6 0 A C SIGUIJ 399 CE2 TYR A  64 2 0 0 220 161 290 A C ATOM 400 CZ TYRA  64 19.744 2.465 44.251 1.00 10.47 A C ANISOU 400 CZ TYR A  64 13141434 1196 −10 −10 0 A C SIGUIJ 400 CZ TYR A  64 2 0 0 220 161 290 A CATOM 401 OH TYR A  64 20.920 2.531 43.518 1.00 10.97 A O ANISOU 401 OHTYR A  64 1338 1250 1217 −13 11 −1 A O SIGUIJ 401 OH TYR A  64 1 0 0 22156 289 A O ATOM 402 C TYR A  64 15.140 2.452 48.882 1.00 10.76 A CANISOU 402 C TYR A  64 1295 1450 1252 −5 1 0 A C SIGUIJ 402 C TYR A  642 0 0 220 161 290 A C ATOM 403 O TYR A  64 15.215 1.388 49.500 1.0011.00 A O ANISOU 403 O TYR A  64 1447 1447 1285 0 5 0 A O SIGUIJ 403 OTYR A  64 1 0 0 221 56 289 A O ATOM 404 N THR A  65 14.050 3.184 48.8081.00 10.90 A N ANISOU 404 N THR A  65 1263 1414 1312 −42 2 1 A N SIGUIJ404 N THR A  65 1 0 0 221 63 289 A N ATOM 405 CA THR A  65 12.729 2.61349.160 1.00 10.94 A C ANISOU 405 CA THR A  65 1275 1602 1189 −104 −15 10A C SIGUIJ 405 CA THR A  65 2 0 0 220 160 290 A C ATOM 406 CB THR A  6512.010 3.507 50.169 1.00 11.44 A C ANISOU 406 CB THR A  65 1538 17581222 54 28 −1 A C SIGUIJ 406 CB THR A  65 2 0 0 220 160 290 A C ATOM 407OG1 THR A  65 12.804 3.542 51.378 1.00 12.76 A O ANISOU 407 OG1 THR A 65 1686 2183 1274 26 −63 −3 A O SIGUIJ 407 OG1 THR A  65 1 0 0 221 56289 A O ATOM 408 CG2 THR A  65 10.601 2.977 50.484 1.00 12.54 A C ANISOU408 CG2 THR A  65 1620 2247 1409 −129 71 −9 A C SIGUIJ 408 CG2 THR A  652 0 0 220 159 290 A C ATOM 409 C THR A  65 11.968 2.489 47.860 1.0010.48 A C ANISOU 409 C THR A  65 1234 1247 1178 1 4 0 A C SIGUIJ 409 CTHR A  65 2 0 0 220 159 290 A C ATOM 410 O THR A  65 11.754 3.485 47.1431.00 10.45 A O ANISOU 410 O THR A  65 1626 1261 1260 −28 −151 11 A OSIGUIJ 410 O THR A  65 1 0 0 221 56 289 A O ATOM 411 N VAL A  66 11.5311.285 47.556 1.00 10.31 A N ANISOU 411 N VAL A  66 1269 1245 1202 −1 5 0A N SIGUIJ 411 N VAL A  66 1 0 0 221 63 289 A N ATOM 412 CA VAL A  6610.826 1.050 46.318 1.00 10.41 A C ANISOU 412 CA VAL A  66 1283 12551218 0 0 0 A C SIGUIJ 412 CA VAL A  66 2 0 0 220 158 290 A C ATOM 413 CBVAL A  66 11.278 −0.305 45.707 1.00 10.27 A C ANISOU 413 CB VAL A  661308 1252 1283 4 2 0 A C SIGUIJ 413 CB VAL A  66 2 0 0 220 158 290 A CATOM 414 CG1 VAL A  66 10.536 −0.512 44.365 1.00 11.03 A C ANISOU 414CG1 VAL A  66 1336 1294 1294 −1 −2 0 A C SIGUIJ 414 CG1 VAL A  66 2 0 0220 157 290 A C ATOM 415 CG2 VAL A  66 12.791 −0.328 45.524 1.00 11.29 AC ANISOU 415 CG2 VAL A  66 1317 1501 2141 14 95 −6 A C SIGUIJ 415 CG2VAL A  66 2 0 0 220 157 290 A C ATOM 416 C VAL A  66 9.323 1.056 46.5491.00 10.46 A C ANISOU 416 C VAL A  66 1281 1388 1207 29 −3 0 A C SIGUIJ416 C VAL A  66 2 0 0 220 157 290 A C ATOM 417 O VAL A  66 8.809 0.33847.437 1.00 10.81 A O ANISOU 417 O VAL A  66 1451 1425 1233 4 54 6 A OSIGUIJ 417 O VAL A  66 1 0 0 221 56 289 A O ATOM 418 N HIS A  67 8.6071.884 45.793 1.00 10.18 A N ANISOU 418 N HIS A  67 1194 1341 1212 −9 0 0A N SIGUIJ 418 N HIS A  67 1 0 0 221 63 289 A N ATOM 419 CA HIS A  677.143 1.919 45.767 1.00 10.17 A C ANISOU 419 CA HIS A  67 1196 1244 1298−1 −5 0 A C SIGUIJ 419 CA HIS A  67 2 0 0 220 156 290 A C ATOM 420 CBHIS A  67 6.708 3.371 45.496 1.00 10.26 A C ANISOU 420 CB HIS A  67 12321246 1435 0 2 0 A C SIGUIJ 420 CB HIS A  67 2 0 0 220 156 290 A C ATOM421 CG HIS A  67 5.308 3.503 44.984 1.00 10.76 A C ANISOU 421 CG HIS A 67 1245 1194 1533 −2 −28 1 A C SIGUIJ 421 CG HIS A  67 2 0 0 220 155290 A C ATOM 422 CD2 HIS A  67 4.768 3.234 43.783 1.00 10.31 A C ANISOU422 CD2 HIS A  67 1216 1250 1538 −1 −17 0 A C SIGUIJ 422 CD2 HIS A  67 20 0 220 155 290 A C ATOM 423 ND1 HIS A  67 4.294 4.012 45.769 1.00 11.12A N ANISOU 423 ND1 HIS A  67 1360 1233 1686 3 107 3 A N SIGUIJ 423 ND1HIS A  67 1 0 0 221 63 289 A N ATOM 424 CE1 HIS A  67 3.182 4.034 45.0611.00 10.85 A C ANISOU 424 CE1 HIS A  67 1383 1465 1735 17 71 −9 A CSIGUIJ 424 CE1 HIS A  67 2 0 0 220 155 290 A C ATOM 425 NE2 HIS A  673.436 3.561 43.858 1.00 10.92 A N ANISOU 425 NE2 HIS A  67 1229 14171718 61 2 0 A N SIGUIJ 425 NE2 HIS A  67 1 0 0 221 63 289 A N ATOM 426 CHIS A  67 6.627 1.015 44.664 1.00 10.07 A C ANISOU 426 C HIS A  67 11581224 1269 1 3 0 A C SIGUIJ 426 C HIS A  67 2 0 0 220 154 290 A C ATOM427 O HIS A  67 7.046 1.167 43.504 1.00 10.01 A O ANISOU 427 O HIS A  671205 1245 1268 0 7 0 A O SIGUIJ 427 O HIS A  67 1 0 0 221 56 289 A OATOM 428 N LEU A  68 5.689 0.115 45.004 1.00 9.85 A N ANISOU 428 N LEU A 68 1174 1220 1400 0 48 0 A N SIGUIJ 428 N LEU A  68 1 0 0 221 63 289 AN ATOM 429 CA LEU A  68 5.041 −0.761 44.009 1.00 10.06 A C ANISOU 429 CALEU A  68 1254 1218 1423 −5 8 0 A C SIGUIJ 429 CA LEU A  68 2 0 0 220154 290 A C ATOM 430 CB LEU A  68 5.539 −2.229 44.129 1.00 11.11 A CANISOU 430 CB LEU A  68 1414 1239 1632 55 −12 0 A C SIGUIJ 430 CB LEU A 68 2 0 0 220 153 290 A C ATOM 431 CG LEU A  68 7.056 −2.399 44.241 1.0010.33 A C ANISOU 431 CG LEU A  68 1408 1250 1460 60 1 −1 A C SIGUIJ 431CG LEU A  68 2 0 0 220 153 290 A C ATOM 432 CD1 LEU A  68 7.481 −2.43145.695 1.00 11.37 A C ANISOU 432 CD1 LEU A  68 1457 1613 1458 −5 0 0 A CSIGUIJ 432 CD1 LEU A  68 2 0 0 220 153 290 A C ATOM 433 CD2 LEU A  687.459 −3.723 43.526 1.00 11.32 A C ANISOU 433 CD2 LEU A  68 1607 12551485 112 4 2 A C SIGUIJ 433 CD2 LEU A  68 2 0 0 220 152 290 A C ATOM 434C LEU A  68 3.539 −0.772 44.264 1.00 10.57 A C ANISOU 434 C LEU A  681264 1284 1304 0 −2 0 A C SIGUIJ 434 C LEU A  68 2 0 0 220 152 290 A CATOM 435 O LEU A  68 3.091 −0.494 45.394 1.00 10.51 A O ANISOU 435 O LEUA  68 1309 1276 1306 3 0 0 A O SIGUIJ 435 O LEU A  68 1 0 0 221 56 289 AO ATOM 436 N GLY A  69 2.783 −1.092 43.229 1.00 10.50 A N ANISOU 436 NGLY A  69 1270 1244 1298 0 0 0 A N SIGUIJ 436 N GLY A  69 1 0 0 221 63289 A N ATOM 437 CA GLY A  69 1.403 −1.483 43.461 1.00 10.99 A C ANISOU437 CA GLY A  69 1293 1231 1709 0 86 1 A C SIGUIJ 437 CA GLY A  69 1 0 0220 151 290 A C ATOM 438 C GLY A  69 0.398 −0.368 43.576 1.00 11.51 A CANISOU 438 C GLY A  69 1328 1234 1649 2 110 4 A C SIGUIJ 438 C GLY A  691 0 0 220 151 290 A C ATOM 439 O GLY A  69 −0.713 −0.611 44.076 1.0012.48 A O ANISOU 439 O GLY A  69 1428 1370 2142 27 322 166 A O SIGUIJ439 O GLY A  69 1 0 0 221 56 289 A O ATOM 440 N SER A  70 0.747 0.84843.134 1.00 11.57 A N ANISOU 440 N SER A  70 1235 1236 1574 0 24 0 A NSIGUIJ 440 N SER A  70 1 0 0 221 63 289 A N ATOM 441 CA SER A  70 −0.2371.925 43.056 1.00 11.55 A C ANISOU 441 CA SER A  70 1239 1251 1429 0 210 A C SIGUIJ 441 CA SER A  70 1 0 0 220 151 290 A C ATOM 442 CB SER A 70 −0.441 2.619 44.423 1.00 11.96 A C ANISOU 442 CB SER A  70 1738 12851450 −46 94 −11 A C SIGUIJ 442 CB SER A  70 1 0 0 220 150 290 A C ATOM443 OG SER A  70 −1.443 3.618 44.270 1.00 12.98 A O ANISOU 443 OG SER A 70 1764 1288 1593 −48 22 −4 A O SIGUIJ 443 OG SER A  70 1 0 0 221 56289 A O ATOM 444 C SER A  70 0.204 2.965 42.058 1.00 11.53 A C ANISOU444 C SER A  70 1228 1259 1420 3 43 −2 A C SIGUIJ 444 C SER A  70 1 0 0220 150 290 A C ATOM 445 O SER A  70 1.350 3.343 41.990 1.00 11.37 A OANISOU 445 O SER A  70 1239 1366 1663 −21 49 5 A O SIGUIJ 445 O SER A 70 1 0 0 221 56 289 A O ATOM 446 N ASP A  71 −0.770 3.521 41.354 1.0011.71 A N ANISOU 446 N ASP A  71 1281 1265 1534 0 −31 0 A N SIGUIJ 446 NASP A  71 1 0 0 221 63 289 A N ATOM 447 CA ASP A  71 −0.489 4.711 40.5341.00 12.03 A C ANISOU 447 CA ASP A  71 1427 1275 1596 9 48 6 A C SIGUIJ447 CA ASP A  71 1 0 0 220 150 290 A C ATOM 448 CB ASP A  71 −1.6044.894 39.509 1.00 13.40 A C ANISOU 448 CB ASP A  71 1546 1920 1725 110−53 22 A C SIGUIJ 448 CB ASP A  71 1 0 0 220 149 290 A C ATOM 449 CG ASPA  71 −1.791 3.679 38.665 1.00 14.52 A C ANISOU 449 CG ASP A  71 19031952 1767 18 12 −1 A C SIGUIJ 449 CG ASP A  71 1 0 0 220 149 290 A CATOM 450 OD1 ASP A  71 −0.769 3.147 38.164 1.00 14.88 A O ANISOU 450 OD1ASP A  71 1891 1928 1789 −5 18 1 A O SIGUIJ 450 OD1 ASP A  71 1 0 0 22156 289 A O ATOM 451 OD2 ASP A  71 −2.933 3.147 38.541 1.00 16.44 A OANISOU 451 OD2 ASP A  71 2055 2638 2741 −297 −69 −29 A O SIGUIJ 451 OD2ASP A  71 1 0 0 221 56 289 A O ATOM 452 C ASP A  71 −0.334 5.983 41.3661.00 12.00 A C ANISOU 452 C ASP A  71 1593 1286 1589 18 0 0 A C SIGUIJ452 C ASP A  71 1 0 0 220 148 290 A C ATOM 453 O ASP A  71 0.092 7.01440.822 1.00 11.57 A O ANISOU 453 O ASP A  71 1416 1223 1748 205 222 23 AO SIGUIJ 453 O ASP A  71 1 0 0 221 56 289 A O ATOM 454 N THR A  72−0.589 5.932 42.678 1.00 11.84 A N ANISOU 454 N THR A  72 1627 1334 1591167 1 2 A N SIGUIJ 454 N THR A  72 1 0 0 221 63 289 A N ATOM 455 CA THRA  72 −0.466 7.136 43.527 1.00 11.99 A C ANISOU 455 CA THR A  72 12681356 1575 −7 322 0 A C SIGUIJ 455 CA THR A  72 1 0 0 220 148 290 A CATOM 456 CB THR A  72 −1.802 7.379 44.280 1.00 12.04 A C ANISOU 456 CBTHR A  72 1289 1617 1621 29 345 −17 A C SIGUIJ 456 CB THR A  72 1 0 0220 148 290 A C ATOM 457 OG1 THR A  72 −2.851 7.509 43.306 1.00 12.69 AO ANISOU 457 OG1 THR A  72 1472 1832 1826 116 159 −45 A O SIGUIJ 457 OG1THR A  72 1 0 0 221 56 289 A O ATOM 458 CG2 THR A  72 −1.690 8.60745.139 1.00 12.47 A C ANISOU 458 CG2 THR A  72 1869 1575 1577 163 78 38A C SIGUIJ 458 CG2 THR A  72 1 0 0 220 147 290 A C ATOM 459 C THR A  720.680 6.999 44.523 1.00 12.26 A C ANISOU 459 C THR A  72 1391 1326 17780 167 −1 A C SIGUIJ 459 C THR A  72 1 0 0 220 147 290 A C ATOM 460 O THRA  72 0.670 6.113 45.375 1.00 12.26 A O ANISOU 460 O THR A  72 1528 13401812 14 190 14 A O SIGUIJ 460 O THR A  72 1 0 0 221 56 289 A O ATOM 461N LEU A  73 1.680 7.883 44.462 1.00 12.60 A N ANISOU 461 N LEU A  731402 1339 1916 −10 225 −38 A N SIGUIJ 461 N LEU A  73 1 0 0 221 63 289 AN ATOM 462 CA LEU A  73 2.735 7.884 45.504 1.00 13.57 A C ANISOU 462 CALEU A  73 1418 1628 1928 −59 214 36 A C SIGUIJ 462 CA LEU A  73 1 0 0220 147 290 A C ATOM 463 CB LEU A  73 3.846 8.880 45.130 1.00 14.14 A CANISOU 463 CB LEU A  73 1465 1597 2415 −28 407 22 A C SIGUIJ 463 CB LEUA  73 1 0 0 220 146 290 A C ATOM 464 CG LEU A  73 4.664 8.540 43.8671.00 13.84 A C ANISOU 464 CG LEU A  73 1301 1722 2343 0 289 3 A C SIGUIJ464 CG LEU A  73 1 0 0 220 146 290 A C ATOM 465 CD1 LEU A  73 5.7309.650 43.616 1.00 14.45 A C ANISOU 465 CD1 LEU A  73 1792 2224 2208 −505131 111 A C SIGUIJ 465 CD1 LEU A  73 1 0 0 220 146 290 A C ATOM 466 CD2LEU A  73 5.275 7.165 43.926 1.00 13.66 A C ANISOU 466 CD2 LEU A  731572 1774 1998 116 193 −65 A C SIGUIJ 466 CD2 LEU A  73 1 0 0 220 145290 A C ATOM 467 C LEU A  73 2.146 8.248 46.864 1.00 14.07 A C ANISOU467 C LEU A  73 1415 1764 1928 −28 196 10 A C SIGUIJ 467 C LEU A  73 1 00 220 145 290 A C ATOM 468 O LEU A  73 1.291 9.145 46.949 1.00 14.84 A OANISOU 468 O LEU A  73 1604 1916 2178 129 180 −51 A O SIGUIJ 468 O LEU A 73 1 0 0 221 56 289 A O ATOM 469 N GLY A  76 2.573 7.558 47.894 1.0014.43 A N ANISOU 469 N GLY A  76 1813 1793 1988 0 31 0 A N SIGUIJ 469 NGLY A  76 1 0 0 221 63 289 A N ATOM 470 CA GLY A  76 2.029 7.757 49.2271.00 14.66 A C ANISOU 470 CA GLY A  76 1744 1834 1985 −30 8 2 A C SIGUIJ470 CA GLY A  76 1 0 0 220 145 290 A C ATOM 471 C GLY A  76 0.747 6.99049.509 1.00 14.25 A C ANISOU 471 C GLY A  76 1721 1756 1856 −5 −26 −3 AC SIGUIJ 471 C GLY A  76 1 0 0 220 144 290 A C ATOM 472 O GLY A  760.269 7.028 50.633 1.00 14.94 A O ANISOU 472 O GLY A  76 1824 2245 187536 13 −5 A O SIGUIJ 472 O GLY A  76 1 0 0 221 56 289 A O ATOM 473 N ASPA  77 0.159 6.340 48.523 1.00 13.69 A N ANISOU 473 N ASP A  77 1317 16371787 112 135 −36 A N SIGUIJ 473 N ASP A  77 1 0 0 221 63 289 A N ATOM474 CA ASP A  77 −1.065 5.558 48.748 1.00 13.68 A C ANISOU 474 CA ASP A 77 1253 1499 1497 188 60 −38 A C SIGUIJ 474 CA ASP A  77 1 0 0 220 144290 A C ATOM 475 CB ASP A  77 −1.328 4.788 47.449 1.00 13.39 A C ANISOU475 CB ASP A  77 1275 1491 1499 144 77 −42 A C SIGUIJ 475 CB ASP A  77 10 0 220 144 290 A C ATOM 476 CG ASP A  77 −2.624 3.983 47.429 1.00 13.49A C ANISOU 476 CG ASP A  77 1298 1594 1652 81 69 −17 A C SIGUIJ 476 CGASP A  77 1 0 0 220 143 290 A C ATOM 477 OD1 ASP A  77 −3.249 3.76348.497 1.00 13.62 A O ANISOU 477 OD1 ASP A  77 1608 1673 1756 27 252 −26A O SIGUIJ 477 OD1 ASP A  77 1 0 0 221 56 289 A O ATOM 478 OD2 ASP A  77−3.016 3.557 46.318 1.00 14.34 A O ANISOU 478 OD2 ASP A  77 1858 19271673 −312 −4 14 A O SIGUIJ 478 OD2 ASP A  77 1 0 0 221 56 289 A O ATOM479 C ASP A  77 −0.798 4.565 49.902 1.00 14.30 A C ANISOU 479 C ASP A 77 1373 1544 1509 164 23 −19 A C SIGUIJ 479 C ASP A  77 1 0 0 220 143290 A C ATOM 480 O ASP A  77 0.222 3.792 49.856 1.00 14.35 A O ANISOU480 O ASP A  77 1562 1823 1918 397 35 −31 A O SIGUIJ 480 O ASP A  77 1 00 221 56 289 A O ATOM 481 N ARG A  78 −1.655 4.557 50.920 1.00 14.71 A NANISOU 481 N ARG A  78 1452 1639 1527 128 77 −58 A N SIGUIJ 481 N ARG A 78 1 0 0 221 63 289 A N ATOM 482 CA ARG A  78 −1.464 3.618 52.022 1.0016.17 A C ANISOU 482 CA ARG A  78 2269 1750 1601 287 65 28 A C SIGUIJ482 CA ARG A  78 1 0 0 220 143 290 A C ATOM 483 CB ARG A  78 −2.5293.871 53.099 1.00 17.47 A C ANISOU 483 CB ARG A  78 2312 2487 1606 46461 16 A C SIGUIJ 483 CB ARG A  78 1 0 0 220 142 290 A C ATOM 484 CG ARGA  78 −2.395 5.237 53.737 1.00 19.88 A C ANISOU 484 CG ARG A  78 41812508 1646 282 71 10 A C SIGUIJ 484 CG ARG A  78 1 0 0 220 142 290 A CATOM 485 CD ARG A  78 −2.622 5.235 55.222 1.00 22.19 A C ANISOU 485 CDARG A  78 9298 12495 1770 143 854 5 A C SIGUIJ 485 CD ARG A  78 1 0 0220 142 290 A C ATOM 486 NE ARG A  78 −2.002 6.444 55.777 1.00 24.36 A NANISOU 486 NE ARG A  78 12217 12616 5189 −25 −2043 −76 A N SIGUIJ 486 NEARG A  78 1 0 0 221 63 289 A N ATOM 487 CZ ARG A  78 −2.465 7.108 56.8411.00 24.83 A C ANISOU 487 CZ ARG A  78 12396 12449 5150 1 −1980 33 A CSIGUIJ 487 CZ ARG A  78 1 0 0 220 141 290 A C ATOM 488 NH1 ARG A  78−3.552 6.670 57.451 1.00 25.75 A N ANISOU 488 NH1 ARG A  78 13703 124699248 −20 334 −1 A N SIGUIJ 488 NH1 ARG A  78 1 0 0 221 63 289 A N ATOM489 NH2 ARG A  78 −1.838 8.192 57.300 1.00 25.77 A N ANISOU 489 NH2 ARGA  78 10587 12383 2300 134 175 −3 A N SIGUIJ 489 NH2 ARG A  78 1 0 0 22163 289 A N ATOM 490 C ARG A  78 −1.544 2.178 51.552 1.00 16.15 A CANISOU 490 C ARG A  78 1423 1795 2007 264 272 −124 A C SIGUIJ 490 C ARGA  78 1 0 0 220 141 290 A C ATOM 491 O ARG A  78 −1.031 1.267 52.2691.00 16.98 A O ANISOU 491 O ARG A  78 2446 2180 2451 659 47 112 A OSIGUIJ 491 O ARG A  78 1 0 0 221 56 289 A O ATOM 492 N ARG A  79 −2.1721.901 50.414 1.00 16.20 A N ANISOU 492 N ARG A  79 1402 1810 1951 −7 32719 A N SIGUIJ 492 N ARG A  79 1 0 0 221 63 289 A N ATOM 493 CA ARG A  79−2.289 0.528 49.913 1.00 16.42 A C ANISOU 493 CA ARG A  79 1569 18272088 26 234 −31 A C SIGUIJ 493 CA ARG A  79 1 0 0 220 141 290 A C ATOM494 CB ARG A  79 −3.446 0.379 48.938 1.00 17.75 A C ANISOU 494 CB ARG A 79 2015 2016 2694 −8 −291 −5 A C SIGUIJ 494 CB ARG A  79 1 0 0 220 141290 A C ATOM 495 CG ARG A  79 −4.772 0.900 49.454 1.00 19.73 A C ANISOU495 CG ARG A  79 2352 2502 4693 128 447 −122 A C SIGUIJ 495 CG ARG A  791 0 0 220 140 290 A C ATOM 496 CD ARG A  79 −5.852 0.878 48.382 1.0021.61 A C ANISOU 496 CD ARG A  79 2995 3034 5338 −6 −194 −6 A C SIGUIJ496 CD ARG A  79 1 0 0 220 140 290 A C ATOM 497 NE ARG A  79 −5.7281.918 47.348 1.00 23.13 A N ANISOU 497 NE ARG A  79 2535 3036 5331 −8−269 −3 A N SIGUIJ 497 NE ARG A  79 1 0 0 221 63 289 A N ATOM 498 CZ ARGA  79 −5.263 1.690 46.132 1.00 22.93 A C ANISOU 498 CZ ARG A  79 35352972 5475 −31 109 −1 A C SIGUIJ 498 CZ ARG A  79 1 0 0 220 140 290 A CATOM 499 NH1 ARG A  79 −4.840 0.456 45.833 1.00 24.17 A N ANISOU 499 NH1ARG A  79 13175 4146 5369 3344 −187 −71 A N SIGUIJ 499 NH1 ARG A  79 1 00 221 63 289 A N ATOM 500 NH2 ARG A  79 −5.275 2.636 45.196 1.00 23.78 AN ANISOU 500 NH2 ARG A  79 2347 2953 5443 101 254 −27 A N SIGUIJ 500 NH2ARG A  79 1 0 0 221 63 289 A N ATOM 501 C ARG A  79 −1.034 0.098 49.1301.00 15.58 A C ANISOU 501 C ARG A  79 1606 1618 2236 0 327 12 A C SIGUIJ501 C ARG A  79 1 0 0 220 139 290 A C ATOM 502 O ARG A  79 −0.912 −1.08748.742 1.00 15.65 A O ANISOU 502 O ARG A  79 1870 1615 2332 2 464 5 A OSIGUIJ 502 O ARG A  79 1 0 0 221 55 289 A O ATOM 503 N ALA A  80 −0.1421.027 48.813 1.00 14.69 A N ANISOU 503 N ALA A  80 1528 1554 1949 42 261−52 A N SIGUIJ 503 N ALA A  80 1 0 0 221 63 289 A N ATOM 504 CA ALA A 80 1.055 0.671 48.028 1.00 13.83 A C ANISOU 504 CA ALA A  80 1362 15391466 101 −41 26 A C SIGUIJ 504 CA ALA A  80 1 0 0 220 139 290 A C ATOM505 CB ALA A  80 1.820 1.914 47.622 1.00 14.11 A C ANISOU 505 CB ALA A 80 1648 1594 1901 3 210 16 A C SIGUIJ 505 CB ALA A  80 1 0 0 220 139290 A C ATOM 506 C ALA A  80 1.967 −0.207 48.880 1.00 13.53 A C ANISOU506 C ALA A  80 1254 1447 1366 57 32 −12 A C SIGUIJ 506 C ALA A  80 1 00 220 138 290 A C ATOM 507 O ALA A  80 1.945 −0.152 50.133 1.00 14.15 AO ANISOU 507 O ALA A  80 1894 2156 1364 533 24 17 A O SIGUIJ 507 O ALA A 80 1 0 0 221 55 289 A O ATOM 508 N GLN A  81 2.777 −1.007 48.211 1.0012.88 A N ANISOU 508 N GLN A  81 1164 1353 1355 −3 17 0 A N SIGUIJ 508 NGLN A  81 1 0 0 221 63 289 A N ATOM 509 CA GLN A  81 3.903 −1.702 48.8581.00 12.88 A C ANISOU 509 CA GLN A  81 1258 1538 1457 117 −31 15 A CSIGUIJ 509 CA GLN A  81 1 0 0 220 138 290 A C ATOM 510 CB GLN A  814.243 −2.974 48.113 1.00 13.68 A C ANISOU 510 CB GLN A  81 1628 15571580 178 −15 −23 A C SIGUIJ 510 CB GLN A  81 1 0 0 220 138 290 A C ATOM511 CG GLN A  81 3.280 −4.094 48.365 1.00 14.30 A C ANISOU 511 CG GLN A 81 2118 1938 1820 −259 12 −9 A C SIGUIJ 511 CG GLN A  81 1 0 0 220 138290 A C ATOM 512 CD GLN A  81 3.665 −5.304 47.553 1.00 14.78 A C ANISOU512 CD GLN A  81 2410 1963 1852 −203 54 −20 A C SIGUIJ 512 CD GLN A  811 0 0 220 137 290 A C ATOM 513 OE1 GLN A  81 4.755 −5.840 47.685 1.0014.65 A O ANISOU 513 OE1 GLN A  81 2285 1532 1692 −435 53 −31 A O SIGUIJ513 OE1 GLN A  81 1 0 0 221 55 289 A O ATOM 514 NE2 GLN A  81 2.772−5.731 46.694 1.00 15.20 A N ANISOU 514 NE2 GLN A  81 2594 1610 2068 −72−186 19 A N SIGUIJ 514 NE2 GLN A  81 1 0 0 221 63 289 A N ATOM 515 C GLNA  81 5.107 −0.798 48.860 1.00 12.83 A C ANISOU 515 C GLN A  81 12721621 1317 87 1 −1 A C SIGUIJ 515 C GLN A  81 1 0 0 220 137 290 A C ATOM516 O GLN A  81 5.399 −0.130 47.854 1.00 13.03 A O ANISOU 516 O GLN A 81 1658 1744 1347 −33 49 8 A O SIGUIJ 516 O GLN A  81 1 0 0 221 55 289A O ATOM 517 N ARG A  82 5.822 −0.751 49.982 1.00 12.82 A N ANISOU 517 NARG A  82 1266 1962 1310 69 0 0 A N SIGUIJ 517 N ARG A  82 1 0 0 221 63289 A N ATOM 518 CA ARG A  82 7.114 −0.102 50.076 1.00 13.15 A C ANISOU518 CA ARG A  82 1298 2122 1292 −4 1 19 A C SIGUIJ 518 CA ARG A  82 1 00 220 137 290 A C ATOM 519 CB ARG A  82 7.102 1.055 51.076 1.00 13.97 AC ANISOU 519 CB ARG A  82 1542 2195 1404 −74 89 −71 A C SIGUIJ 519 CBARG A  82 1 0 0 220 136 290 A C ATOM 520 CG ARG A  82 6.258 2.217 50.6051.00 15.61 A C ANISOU 520 CG ARG A  82 1860 2364 1795 128 −3 −4 A CSIGUIJ 520 CG ARG A  82 1 0 0 220 136 290 A C ATOM 521 CD ARG A  825.972 3.220 51.759 1.00 17.78 A C ANISOU 521 CD ARG A  82 3912 2325 1887147 488 37 A C SIGUIJ 521 CD ARG A  82 1 0 0 220 136 290 A C ATOM 522 NEARG A  82 7.152 3.801 52.439 1.00 20.13 A N ANISOU 522 NE ARG A  82 44773200 2961 −273 −130 25 A N SIGUIJ 522 NE ARG A  82 1 0 0 221 63 289 A NATOM 523 CZ ARG A  82 7.612 3.635 53.704 1.00 20.42 A C ANISOU 523 CZARG A  82 3283 3539 2778 21 351 −15 A C SIGUIJ 523 CZ ARG A  82 1 0 0220 136 290 A C ATOM 524 NH1 ARG A  82 7.071 2.836 54.659 1.00 21.72 A NANISOU 524 NH1 ARG A  82 2666 3558 2587 15 −6 0 A N SIGUIJ 524 NH1 ARG A 82 1 0 0 221 63 289 A N ATOM 525 NH2 ARG A  82 8.667 4.345 54.040 1.0021.55 A N ANISOU 525 NH2 ARG A  82 3396 3567 3679 −3 60 1 A N SIGUIJ 525NH2 ARG A  82 1 0 0 221 63 289 A N ATOM 526 C ARG A  82 8.125 −1.14250.520 1.00 12.58 A C ANISOU 526 C ARG A  82 1406 2256 1072 133 74 4 A CSIGUIJ 526 C ARG A  82 1 0 0 220 135 290 A C ATOM 527 O ARG A  82 7.855−1.914 51.507 1.00 13.16 A O ANISOU 527 O ARG A  82 1450 2400 1172 188134 113 A O SIGUIJ 527 O ARG A  82 1 0 0 221 55 289 A O ATOM 528 N ILE A 83 9.274 −1.267 49.827 1.00 11.91 A N ANISOU 528 N ILE A  83 1409 17111104 68 86 1 A N SIGUIJ 528 N ILE A  83 1 0 0 221 63 289 A N ATOM 529 CAILE A  83 10.267 −2.294 50.147 1.00 11.49 A C ANISOU 529 CA ILE A  831349 1609 1387 −26 0 0 A C SIGUIJ 529 CA ILE A  83 1 0 0 220 135 290 A CATOM 530 CB ILE A  83 10.238 −3.458 49.116 1.00 11.87 A C ANISOU 530 CBILE A  83 1459 1615 1407 −37 7 −2 A C SIGUIJ 530 CB ILE A  83 1 0 0 220135 290 A C ATOM 531 CG2 ILE A  83 11.302 −4.507 49.456 1.00 12.03 A CANISOU 531 CG2 ILE A  83 1493 1636 1501 −11 0 0 A C SIGUIJ 531 CG2 ILE A 83 1 0 0 220 135 290 A C ATOM 532 CG1 ILE A  83 8.827 −4.068 49.0361.00 11.90 A C ANISOU 532 CG1 ILE A  83 1477 1764 1850 −95 21 6 A CSIGUIJ 532 CG1 ILE A  83 1 0 0 220 134 290 A C ATOM 533 CD1 ILE A  838.669 −5.109 47.983 1.00 12.03 A C ANISOU 533 CD1 ILE A  83 1593 17631886 −7 −62 −2 A C SIGUIJ 533 CD1 ILE A  83 1 0 0 220 134 290 A C ATOM534 C ILE A  83 11.635 −1.625 50.099 1.00 11.35 A C ANISOU 534 C ILE A 83 1318 1448 1310 49 0 0 A C SIGUIJ 534 C ILE A  83 1 0 0 220 134 290 AC ATOM 535 O ILE A  83 12.039 −0.953 49.109 1.00 11.54 A O ANISOU 535 OILE A  83 1387 1486 1327 7 6 0 A O SIGUIJ 535 O ILE A  83 1 0 0 221 55289 A O ATOM 536 N ALYS A  84 12.412 −1.875 51.155 0.50 11.01 A N ANISOU536 N ALYS A  84 1311 1305 1306 0 0 0 A N SIGUIJ 536 N ALYS A  84 1 0 0221 63 289 A N ATOM 537 N BLYS A  84 12.408 −1.860 51.162 0.50 13.20 A NANISOU 537 N BLYS A  84 1313 1284 1307 0 0 0 A N SIGUIJ 537 N BLYS A  841 0 0 221 63 289 A N ATOM 538 CA ALYS A  84 13.788 −1.375 51.216 0.5011.28 A C ANISOU 538 CA ALYS A  84 1318 1319 1231 0 2 0 A C SIGUIJ 538CA ALYS A  84 1 0 0 220 134 290 A C ATOM 539 CA BLYS A  84 13.787 −1.36551.222 0.50 13.47 A C ANISOU 539 CA BLYS A  84 1322 1300 1256 −1 3 0 A CSIGUIJ 539 CA BLYS A  84 1 0 0 220 133 290 A C ATOM 540 CB ALYS A  8414.322 −1.576 52.631 0.50 12.09 A C ANISOU 540 CB ALYS A  84 1460 17371232 119 −21 −2 A C SIGUIJ 540 CB ALYS A  84 1 0 0 220 133 290 A C ATOM541 CB BLYS A  84 14.312 −1.526 52.654 0.50 14.28 A C ANISOU 541 CB BLYSA  84 1368 1464 1254 25 4 0 A C SIGUIJ 541 CB BLYS A  84 1 0 0 220 133290 A C ATOM 542 CG ALYS A  84 15.582 −0.808 52.931 0.50 13.81 A CANISOU 542 CG ALYS A  84 1596 2052 1371 −78 −71 18 A C SIGUIJ 542 CGALYS A  84 1 0 0 220 132 290 A C ATOM 543 CG BLYS A  84 15.719 −0.99352.907 0.50 16.00 A C ANISOU 543 CG BLYS A  84 1422 1806 1303 −104 3 −1A C SIGUIJ 543 CG BLYS A  84 1 0 0 220 132 290 A C ATOM 544 CD ALYS A 84 15.272 0.692 53.048 0.50 15.76 A C ANISOU 544 CD ALYS A  84 17702063 1729 −42 −5 2 A C SIGUIJ 544 CD ALYS A  84 1 0 0 220 132 290 A CATOM 545 CD BLYS A  84 15.824 0.519 52.707 0.50 17.95 A C ANISOU 545 CDBLYS A  84 2138 1820 1735 −173 −167 68 A C SIGUIJ 545 CD BLYS A  84 1 00 220 132 290 A C ATOM 546 CE ALYS A  84 16.490 1.520 53.380 0.50 17.29A C ANISOU 546 CE ALYS A  84 1795 1956 2589 26 −257 21 A C SIGUIJ 546 CEALYS A  84 1 0 0 220 131 290 A C ATOM 547 CE BLYS A  84 14.820 1.32553.515 0.50 19.48 A C ANISOU 547 CE BLYS A  84 2552 2209 2096 105 75 19A C SIGUIJ 547 CE BLYS A  84 1 0 0 220 131 290 A C ATOM 548 NZ ALYS A 84 16.029 2.817 53.936 0.50 18.71 A N ANISOU 548 NZ ALYS A  84 23351993 2853 103 11 0 A N SIGUIJ 548 NZ ALYS A  84 1 0 0 221 63 289 A NATOM 549 NZ BLYS A  84 15.068 1.396 54.997 0.50 20.90 A N ANISOU 549 NZBLYS A  84 3179 3141 2119 1 −31 −1 A N SIGUIJ 549 NZ BLYS A  84 1 0 0221 63 289 A N ATOM 550 C ALYS A  84 14.654 −2.177 50.232 0.50 10.91 A CANISOU 550 C ALYS A  84 1313 1314 1240 0 −1 0 A C SIGUIJ 550 C ALYS A 84 1 0 0 220 131 290 A C ATOM 551 C BLYS A  84 14.659 −2.175 50.2450.50 13.10 A C ANISOU 551 C BLYS A  84 1316 1304 1255 0 0 0 A C SIGUIJ551 C BLYS A  84 1 0 0 220 131 290 A C ATOM 552 O ALYS A  84 14.506−3.403 50.098 0.50 11.25 A O ANISOU 552 O ALYS A  84 1365 1314 1304 −1 20 A O SIGUIJ 552 O ALYS A  84 1 0 0 221 55 289 A O ATOM 553 O BLYS A  8414.502 −3.395 50.108 0.50 13.44 A O ANISOU 553 O BLYS A  84 1409 13051320 −4 2 0 A O SIGUIJ 553 O BLYS A  84 1 0 0 221 55 289 A O ATOM 554 NALA A  85 15.588 −1.496 49.575 1.00 10.86 A N ANISOU 554 N ALA A  851309 1307 1236 0 −6 0 A N SIGUIJ 554 N ALA A  85 1 0 0 221 63 289 A NATOM 555 CA ALA A  85 16.554 −2.127 48.697 1.00 10.85 A C ANISOU 555 CAALA A  85 1332 1285 1263 −5 20 −2 A C SIGUIJ 555 CA ALA A  85 1 0 0 220130 290 A C ATOM 556 CB ALA A  85 16.188 −1.868 47.212 1.00 10.61 A CANISOU 556 CB ALA A  85 1545 1376 1277 −32 −40 6 A C SIGUIJ 556 CB ALA A 85 1 0 0 220 130 290 A C ATOM 557 C ALA A  85 17.920 −1.574 49.010 1.0011.52 A C ANISOU 557 C ALA A  85 1340 1278 1472 −15 −6 0 A C SIGUIJ 557C ALA A  85 1 0 0 220 130 290 A C ATOM 558 O ALA A  85 18.180 −0.36748.811 1.00 11.81 A O ANISOU 558 O ALA A  85 1423 1289 1607 −36 8 0 A OSIGUIJ 558 O ALA A  85 1 0 0 221 55 289 A O ATOM 559 N SER A  86 18.835−2.432 49.461 1.00 11.89 A N ANISOU 559 N SER A  86 1430 1388 1488 81 −11 A N SIGUIJ 559 N SER A  86 1 0 0 221 63 289 A N ATOM 560 CA SER A  8620.157 −1.979 49.872 1.00 12.90 A C ANISOU 560 CA SER A  86 1476 17771455 −50 1 −1 A C SIGUIJ 560 CA SER A  86 1 0 0 220 130 290 A C ATOM 561CB SER A  86 20.636 −2.820 51.051 1.00 13.15 A C ANISOU 561 CB SER A  861981 1880 1582 −59 −228 63 A C SIGUIJ 561 CB SER A  86 1 0 0 220 130 290A C ATOM 562 OG SER A  86 19.800 −2.651 52.157 1.00 14.64 A O ANISOU 562OG SER A  86 2186 2107 1678 −37 −97 22 A O SIGUIJ 562 OG SER A  86 1 0 0221 55 289 A O ATOM 563 C SER A  86 21.190 −2.062 48.745 1.00 13.37 A CANISOU 563 C SER A  86 1473 1707 1453 −43 0 0 A C SIGUIJ 563 C SER A  861 0 0 220 129 290 A C ATOM 564 O SER A  86 22.076 −1.207 48.664 1.0014.89 A O ANISOU 564 O SER A  86 1823 2110 2787 −408 86 46 A O SIGUIJ564 O SER A  86 1 0 0 221 55 289 A O ATOM 565 N LYS A  87 21.103 −3.04847.876 1.00 13.17 A N ANISOU 565 N LYS A  87 1507 1678 1442 −30 0 0 A NSIGUIJ 565 N LYS A  87 1 0 0 221 62 289 A N ATOM 566 CA LYS A  87 22.134−3.292 46.848 1.00 13.39 A C ANISOU 566 CA LYS A  87 1513 1739 1433 22−3 0 A C SIGUIJ 566 CA LYS A  87 1 0 0 220 129 290 A C ATOM 567 CB LYS A 87 22.532 −4.783 46.793 1.00 15.31 A C ANISOU 567 CB LYS A  87 15881756 1988 34 46 −8 A C SIGUIJ 567 CB LYS A  87 1 0 0 220 129 290 A CATOM 568 CG LYS A  87 23.052 −5.301 48.119 1.00 16.98 A C ANISOU 568 CGLYS A  87 1980 2174 2064 209 −66 66 A C SIGUIJ 568 CG LYS A  87 1 0 0220 129 290 A C ATOM 569 CD LYS A  87 23.352 −6.794 47.948 1.00 19.00 AC ANISOU 569 CD LYS A  87 3261 2229 2866 465 −27 −20 A C SIGUIJ 569 CDLYS A  87 1 0 0 220 128 290 A C ATOM 570 CE LYS A  87 23.903 −7.40549.195 1.00 20.42 A C ANISOU 570 CE LYS A  87 3382 3215 2904 1007 191243 A C SIGUIJ 570 CE LYS A  87 1 0 0 220 128 290 A C ATOM 571 NZ LYS A 87 23.646 −8.865 49.145 1.00 22.25 A N ANISOU 571 NZ LYS A  87 84853389 5651 92 1139 −70 A N SIGUIJ 571 NZ LYS A  87 1 0 0 221 62 289 A NATOM 572 C LYS A  87 21.668 −2.897 45.446 1.00 12.69 A C ANISOU 572 CLYS A  87 1309 1533 1428 −82 19 9 A C SIGUIJ 572 C LYS A  87 1 0 0 220128 290 A C ATOM 573 O LYS A  87 20.487 −3.076 45.072 1.00 12.42 A OANISOU 573 O LYS A  87 1335 1510 1674 −77 −56 −16 A O SIGUIJ 573 O LYS A 87 1 0 0 221 55 289 A O ATOM 574 N SER A  88 22.603 −2.427 44.641 1.0011.85 A N ANISOU 574 N SER A  88 1231 1293 1400 33 5 −2 A N SIGUIJ 574 NSER A  88 1 0 0 221 62 289 A N ATOM 575 CA SER A  88 22.302 −2.15743.242 1.00 11.82 A C ANISOU 575 CA SER A  88 1310 1266 1405 0 −4 0 A CSIGUIJ 575 CA SER A  88 1 0 0 220 128 290 A C ATOM 576 CB SER A  8821.699 −0.751 43.109 1.00 11.87 A C ANISOU 576 CB SER A  88 1411 12731611 29 −17 0 A C SIGUIJ 576 CB SER A  88 1 0 0 220 127 290 A C ATOM 577OG SER A  88 22.490 0.270 43.706 1.00 11.43 A O ANISOU 577 OG SER A  881456 1288 1576 −5 −6 0 A O SIGUIJ 577 OG SER A  88 1 0 0 221 55 289 A OATOM 578 C SER A  88 23.561 −2.295 42.397 1.00 11.83 A C ANISOU 578 CSER A  88 1310 1405 1435 14 5 −1 A C SIGUIJ 578 C SER A  88 1 0 0 220127 290 A C ATOM 579 O SER A  88 24.684 −2.165 42.928 1.00 11.99 A OANISOU 579 O SER A  88 1354 1687 1594 −27 −86 −8 A O SIGUIJ 579 O SER A 88 1 0 0 221 55 289 A O ATOM 580 N PHE A  89 23.369 −2.558 41.108 1.0011.41 A N ANISOU 580 N PHE A  89 1224 1344 1444 31 8 −2 A N SIGUIJ 580 NPHE A  89 1 0 0 221 62 289 A N ATOM 581 CA PHE A  89 24.457 −2.97240.208 1.00 11.41 A C ANISOU 581 CA PHE A  89 1236 1359 1516 51 26 −7 AC SIGUIJ 581 CA PHE A  89 1 0 0 220 127 290 A C ATOM 582 CB PHE A  8924.433 −4.489 40.002 1.00 12.08 A C ANISOU 582 CB PHE A  89 1854 13481848 58 0 −2 A C SIGUIJ 582 CB PHE A  89 1 0 0 220 127 290 A C ATOM 583CG PHE A  89 24.452 −5.264 41.298 1.00 12.41 A C ANISOU 583 CG PHE A  891977 1324 1856 87 −10 −4 A C SIGUIJ 583 CG PHE A  89 1 0 0 220 127 290 AC ATOM 584 CD1 PHE A  89 23.290 −5.587 41.963 1.00 13.24 A C ANISOU 584CD1 PHE A  89 2000 1457 1919 49 4 1 A C SIGUIJ 584 CD1 PHE A  89 1 0 0220 126 290 A C ATOM 585 CD2 PHE A  89 25.664 −5.585 41.911 1.00 13.13 AC ANISOU 585 CD2 PHE A  89 2036 1910 1891 269 −31 −35 A C SIGUIJ 585 CD2PHE A  89 1 0 0 220 126 290 A C ATOM 586 CE1 PHE A  89 23.316 −6.18143.191 1.00 13.82 A C ANISOU 586 CE1 PHE A  89 2540 1477 1932 170 45 10A C SIGUIJ 586 CE1 PHE A  89 1 0 0 220 126 290 A C ATOM 587 CE2 PHE A 89 25.653 −6.191 43.178 1.00 13.75 A C ANISOU 587 CE2 PHE A  89 25631950 1900 194 −63 −18 A C SIGUIJ 587 CE2 PHE A  89 1 0 0 220 126 290 A CATOM 588 CZ PHE A  89 24.517 −6.464 43.779 1.00 13.84 A C ANISOU 588 CZPHE A  89 2582 1757 2030 251 1 0 A C SIGUIJ 588 CZ PHE A  89 1 0 0 220125 290 A C ATOM 589 C PHE A  89 24.226 −2.252 38.903 1.00 11.62 A CANISOU 589 C PHE A  89 1222 1245 1445 252 138 −127 A C SIGUIJ 589 C PHEA  89 1 0 0 220 125 290 A C ATOM 590 O PHE A  89 23.326 −2.590 38.1081.00 11.21 A O ANISOU 590 O PHE A  89 1301 1248 1491 213 85 −90 A OSIGUIJ 590 O PHE A  89 1 0 0 221 55 289 A O ATOM 591 N AARG A  90 25.105−1.294 38.630 0.50 12.01 A N ANISOU 591 N AARG A  90 1452 1515 1438 −8 00 A N SIGUIJ 591 N AARG A  90 1 0 0 221 62 289 A N ATOM 592 N BARG A  9025.097 −1.280 38.633 0.50 14.20 A N ANISOU 592 N BARG A  90 1474 15291451 −17 1 0 A N SIGUIJ 592 N BARG A  90 1 0 0 221 62 289 A N ATOM 593CA AARG A  90 25.103 −0.574 37.349 0.50 13.07 A C ANISOU 593 CA AARG A 90 1337 1515 1436 −7 2 0 A C SIGUIJ 593 CA AARG A  90 1 0 0 220 125 290A C ATOM 594 CA BARG A  90 25.092 −0.536 37.359 0.50 15.26 A C ANISOU594 CA BARG A  90 1311 1551 1448 4 4 0 A C SIGUIJ 594 CA BARG A  90 1 00 220 125 290 A C ATOM 595 CB AARG A  90 25.964 0.653 37.398 0.50 13.27A C ANISOU 595 CB AARG A  90 1359 1530 1493 −22 0 0 A C SIGUIJ 595 CBAARG A  90 1 0 0 220 125 290 A C ATOM 596 CB BARG A  90 25.879 0.76637.474 0.50 15.46 A C ANISOU 596 CB BARG A  90 1415 1599 3073 −44 −208−23 A C SIGUIJ 596 CB BARG A  90 1 0 0 220 124 290 A C ATOM 597 CG AARGA  90 25.363 1.765 38.207 0.50 14.09 A C ANISOU 597 CG AARG A  90 13151506 1503 −57 3 1 A C SIGUIJ 597 CG AARG A  90 1 0 0 220 124 290 A CATOM 598 CG BARG A  90 25.238 1.764 38.451 0.50 16.28 A C ANISOU 598 CGBARG A  90 1597 1623 3101 −3 −141 −7 A C SIGUIJ 598 CG BARG A  90 1 0 0220 124 290 A C ATOM 599 CD AARG A  90 26.399 2.861 38.297 0.50 15.12 AC ANISOU 599 CD AARG A  90 1180 1377 1504 72 7 −2 A C SIGUIJ 599 CD AARGA  90 1 0 0 220 124 290 A C ATOM 600 CD BARG A  90 26.049 3.043 38.6680.50 17.31 A C ANISOU 600 CD BARG A  90 1713 1622 4341 −7 −565 48 A CSIGUIJ 600 CD BARG A  90 1 0 0 220 124 290 A C ATOM 601 NE AARG A  9025.790 4.161 38.571 0.50 15.48 A N ANISOU 601 NE AARG A  90 1129 13621352 52 −16 3 A N SIGUIJ 601 NE AARG A  90 1 0 0 221 62 289 A N ATOM 602NE BARG A  90 27.405 2.748 39.094 0.50 17.67 A N ANISOU 602 NE BARG A 90 1618 2442 3049 156 −166 24 A N SIGUIJ 602 NE BARG A  90 1 0 0 221 62289 A N ATOM 603 CZ AARG A  90 26.464 5.249 38.929 0.50 15.12 A C ANISOU603 CZ AARG A  90 1156 1371 1291 30 21 −4 A C SIGUIJ 603 CZ AARG A  90 10 0 220 123 290 A C ATOM 604 CZ BARG A  90 28.397 3.628 39.073 0.5017.31 A C ANISOU 604 CZ BARG A  90 1654 2495 3133 110 −154 16 A C SIGUIJ604 CZ BARG A  90 1 0 0 220 123 290 A C ATOM 605 NH1 AARG A  90 27.7895.187 39.088 0.50 15.97 A N ANISOU 605 NH1 AARG A  90 1171 1391 2259 29−89 6 A N SIGUIJ 605 NH1 AARG A  90 1 0 0 221 62 289 A N ATOM 606 NH1BARG A  90 28.185 4.878 38.667 0.50 18.16 A N ANISOU 606 NH1 BARG A  901573 2490 3114 82 −178 12 A N SIGUIJ 606 NH1 BARG A  90 1 0 0 221 62 289A N ATOM 607 NH2 AARG A  90 25.818 6.401 39.026 0.50 14.36 A N ANISOU607 NH2 AARG A  90 780 1244 886 −183 9 8 A N SIGUIJ 607 NH2 AARG A  90 10 0 221 62 289 A N ATOM 608 NH2 BARG A  90 29.620 3.219 39.394 0.5016.55 A N ANISOU 608 NH2 BARG A  90 1599 2618 2127 159 98 −22 A N SIGUIJ608 NH2 BARG A  90 1 0 0 221 62 289 A N ATOM 609 C AARG A  90 25.703−1.419 36.246 0.50 13.71 A C ANISOU 609 C AARG A  90 1376 1535 1437 1913 −3 A C SIGUIJ 609 C AARG A  90 1 0 0 220 123 290 A C ATOM 610 C BARGA  90 25.739 −1.352 36.246 0.50 15.90 A C ANISOU 610 C BARG A  90 13751581 1444 51 8 −4 A C SIGUIJ 610 C BARG A  90 1 0 0 220 123 290 A C ATOM611 O AARG A  90 26.568 −2.275 36.492 0.50 13.91 A O ANISOU 611 O AARG A 90 1717 1882 1575 358 3 36 A O SIGUIJ 611 O AARG A  90 1 0 0 221 55 289A O ATOM 612 O BARG A  90 26.653 −2.145 36.490 0.50 16.10 A O ANISOU 612O BARG A  90 1656 1911 2112 331 −111 76 A O SIGUIJ 612 O BARG A  90 1 00 221 55 289 A O ATOM 613 N HIS A  91 25.256 −1.184 35.020 1.00 14.41 AN ANISOU 613 N HIS A  91 1453 1903 1440 182 −1 5 A N SIGUIJ 613 N HIS A 91 1 0 0 221 62 289 A N ATOM 614 CA HIS A  91 25.955 −1.767 33.871 1.0015.48 A C ANISOU 614 CA HIS A  91 1577 2114 1439 328 2 8 A C SIGUIJ 614CA HIS A  91 1 0 0 220 123 290 A C ATOM 615 CB HIS A  91 25.243 −1.34232.609 1.00 15.53 A C ANISOU 615 CB HIS A  91 1692 2116 1439 400 −21 −23A C SIGUIJ 615 CB HIS A  91 1 0 0 220 122 290 A C ATOM 616 CG HIS A  9125.732 −2.054 31.364 1.00 16.17 A C ANISOU 616 CG HIS A  91 2080 20391478 403 112 14 A C SIGUIJ 616 CG HIS A  91 1 0 0 220 122 290 A C ATOM617 CD2 HIS A  91 25.170 −3.049 30.632 1.00 16.53 A C ANISOU 617 CD2 HISA  91 2575 2179 1489 112 120 22 A C SIGUIJ 617 CD2 HIS A  91 1 0 0 220122 290 A C ATOM 618 ND1 HIS A  91 26.940 −1.752 30.760 1.00 16.33 A NANISOU 618 ND1 HIS A  91 2208 2709 1805 237 296 −14 A N SIGUIJ 618 ND1HIS A  91 1 0 0 221 62 289 A N ATOM 619 CE1 HIS A  91 27.098 −2.55129.707 1.00 16.71 A C ANISOU 619 CE1 HIS A  91 3168 2580 1781 149 530 68A C SIGUIJ 619 CE1 HIS A  91 1 0 0 220 122 290 A C ATOM 620 NE2 HIS A 91 26.049 −3.343 29.609 1.00 16.79 A N ANISOU 620 NE2 HIS A  91 30362323 1757 343 466 148 A N SIGUIJ 620 NE2 HIS A  91 1 0 0 221 62 289 A NATOM 621 C HIS A  91 27.399 −1.213 33.878 1.00 16.12 A C ANISOU 621 CHIS A  91 1549 1980 1755 379 51 −52 A C SIGUIJ 621 C HIS A  91 1 0 0 220122 290 A C ATOM 622 O HIS A  91 27.633 −0.033 34.149 1.00 15.90 A OANISOU 622 O HIS A  91 1630 2027 2064 291 356 −175 A O SIGUIJ 622 O HISA  91 1 0 0 221 55 289 A O ATOM 623 N PRO A  92 28.377 −2.096 33.5681.00 17.08 A N ANISOU 623 N PRO A  92 1599 1960 2747 346 307 −122 A NSIGUIJ 623 N PRO A  92 1 0 0 221 62 289 A N ATOM 624 CD PRO A  92 28.200−3.528 33.228 1.00 17.34 A C ANISOU 624 CD PRO A  92 1555 1964 2959 352421 −171 A C SIGUIJ 624 CD PRO A  92 1 0 0 220 121 290 A C ATOM 625 CAPRO A  92 29.789 −1.732 33.662 1.00 18.05 A C ANISOU 625 CA PRO A  921637 2575 3230 178 267 −45 A C SIGUIJ 625 CA PRO A  92 1 0 0 220 121 290A C ATOM 626 CB PRO A  92 30.523 −3.039 33.352 1.00 18.03 A C ANISOU 626CB PRO A  92 2147 2595 5347 238 1218 −26 A C SIGUIJ 626 CB PRO A  92 1 00 220 121 290 A C ATOM 627 CG PRO A  92 29.595 −3.943 32.745 1.00 17.85A C ANISOU 627 CG PRO A  92 1886 2564 5684 469 1307 −351 A C SIGUIJ 627CG PRO A  92 1 0 0 220 121 290 A C ATOM 628 C PRO A  92 30.261 −0.61432.741 1.00 18.73 A C ANISOU 628 C PRO A  92 2870 2518 3323 60 795 −195A C SIGUIJ 628 C PRO A  92 1 0 0 220 121 290 A C ATOM 629 O PRO A  9231.335 0.019 32.997 1.00 19.68 A O ANISOU 629 O PRO A  92 3289 3223 3753−484 378 338 A O SIGUIJ 629 O PRO A  92 1 0 0 221 55 289 A O ATOM 630 NGLY A  93 29.503 −0.367 31.687 1.00 19.18 A N ANISOU 630 N GLY A  932405 2455 3056 209 1157 −308 A N SIGUIJ 630 N GLY A  93 1 0 0 221 62 289A N ATOM 631 CA GLY A  93 29.954 0.623 30.716 1.00 19.61 A C ANISOU 631CA GLY A  93 2978 2883 3679 249 1468 152 A C SIGUIJ 631 CA GLY A  93 1 00 220 120 290 A C ATOM 632 C GLY A  93 29.473 2.046 30.978 1.00 19.41 AC ANISOU 632 C GLY A  93 2053 2902 1983 215 −4 −11 A C SIGUIJ 632 C GLYA  93 1 0 0 220 120 290 A C ATOM 633 O GLY A  93 29.597 2.921 30.1121.00 19.30 A O ANISOU 633 O GLY A  93 1718 2790 1916 404 188 −106 A OSIGUIJ 633 O GLY A  93 1 0 0 221 55 289 A O ATOM 634 N TYR A  94 28.8712.295 32.157 1.00 19.65 A N ANISOU 634 N TYR A  94 2158 3387 1987 465 −3−8 A N SIGUIJ 634 N TYR A  94 1 0 0 221 62 289 A N ATOM 635 CA TYR A  9428.106 3.547 32.315 1.00 19.52 A C ANISOU 635 CA TYR A  94 1425 31061812 5 30 4 A C SIGUIJ 635 CA TYR A  94 1 0 0 220 120 290 A C ATOM 636CB TYR A  94 27.215 3.525 33.587 1.00 18.03 A C ANISOU 636 CB TYR A  941488 2218 1833 0 63 0 A C SIGUIJ 636 CB TYR A  94 1 0 0 220 120 290 A CATOM 637 CG TYR A  94 26.540 4.842 33.886 1.00 16.64 A C ANISOU 637 CGTYR A  94 1190 2118 1697 −176 81 21 A C SIGUIJ 637 CG TYR A  94 1 0 0220 120 290 A C ATOM 638 CD1 TYR A  94 25.670 5.431 32.967 1.00 16.20 AC ANISOU 638 CD1 TYR A  94 1200 1798 1785 −351 −38 −20 A C SIGUIJ 638CD1 TYR A  94 1 0 0 220 119 290 A C ATOM 639 CE1 TYR A  94 25.003 6.63333.222 1.00 15.88 A C ANISOU 639 CE1 TYR A  94 1296 1798 1741 −327 89 53A C SIGUIJ 639 CE1 TYR A  94 1 0 0 220 119 290 A C ATOM 640 CD2 TYR A 94 26.765 5.484 35.089 1.00 16.08 A C ANISOU 640 CD2 TYR A  94 16832145 1718 −218 4 7 A C SIGUIJ 640 CD2 TYR A  94 1 0 0 220 119 290 A CATOM 641 CE2 TYR A  94 26.156 6.678 35.380 1.00 15.75 A C ANISOU 641 CE2TYR A  94 1824 2177 1776 −145 0 0 A C SIGUIJ 641 CE2 TYR A  94 1 0 0 220119 290 A C ATOM 642 CZ TYR A  94 25.269 7.255 34.455 1.00 15.56 A CANISOU 642 CZ TYR A  94 1649 1854 1770 −374 23 31 A C SIGUIJ 642 CZ TYRA  94 1 0 0 220 119 290 A C ATOM 643 OH TYR A  94 24.616 8.431 34.7131.00 16.26 A O ANISOU 643 OH TYR A  94 2237 2035 1910 −48 22 −4 A OSIGUIJ 643 OH TYR A  94 1 0 0 221 55 289 A O ATOM 644 C TYR A  94 28.9944.752 32.342 1.00 20.49 A C ANISOU 644 C TYR A  94 1698 3273 2675 −20515 2 A C SIGUIJ 644 C TYR A  94 1 0 0 220 119 290 A C ATOM 645 O TYR A 94 29.967 4.779 33.096 1.00 20.98 A O ANISOU 645 O TYR A  94 1824 40792897 −213 −149 −19 A O SIGUIJ 645 O TYR A  94 1 0 0 221 55 289 A O ATOM646 N SER A  95 28.623 5.734 31.536 1.00 21.52 A N ANISOU 646 N SER A 95 1637 3332 2624 −119 145 13 A N SIGUIJ 646 N SER A  95 1 0 0 221 62289 A N ATOM 647 CA SER A  95 29.362 6.989 31.443 1.00 22.67 A C ANISOU647 CA SER A  95 2089 3501 3158 −388 156 47 A C SIGUIJ 647 CA SER A  951 0 0 220 118 290 A C ATOM 648 CB SER A  95 29.691 7.323 29.984 1.0022.92 A C ANISOU 648 CB SER A  95 2562 2915 3189 −9 350 −2 A C SIGUIJ648 CB SER A  95 1 0 0 220 118 290 A C ATOM 649 OG SER A  95 30.3498.587 29.868 1.00 23.39 A O ANISOU 649 OG SER A  95 2664 2945 3663 −58370 36 A O SIGUIJ 649 OG SER A  95 1 0 0 221 55 289 A O ATOM 650 C SER A 95 28.503 8.103 31.972 1.00 23.35 A C ANISOU 650 C SER A  95 2613 39172845 123 −66 22 A C SIGUIJ 650 C SER A  95 1 0 0 220 118 290 A C ATOM651 O SER A  95 27.447 8.418 31.383 1.00 23.22 A O ANISOU 651 O SER A 95 2406 2721 2567 −271 111 96 A O SIGUIJ 651 O SER A  95 1 0 0 221 55289 A O ATOM 652 N THR A  96 28.986 8.760 33.015 1.00 24.40 A N ANISOU652 N THR A  96 2502 3902 2847 184 −57 18 A N SIGUIJ 652 N THR A  96 1 00 221 62 289 A N ATOM 653 CA THR A  96 28.311 9.981 33.445 1.00 25.35 AC ANISOU 653 CA THR A  96 3199 4099 4076 423 382 −155 A C SIGUIJ 653 CATHR A  96 1 0 0 220 118 290 A C ATOM 654 CB THR A  96 28.954 10.61334.718 1.00 25.49 A C ANISOU 654 CB THR A  96 4324 4243 4194 7 9 1 A CSIGUIJ 654 CB THR A  96 1 0 0 220 118 290 A C ATOM 655 OG1 THR A  9630.207 11.246 34.389 1.00 26.34 A O ANISOU 655 OG1 THR A  96 4383 42665130 8 242 12 A O SIGUIJ 655 OG1 THR A  96 1 0 0 221 55 289 A O ATOM 656CG2 THR A  96 29.150 9.564 35.786 1.00 25.75 A C ANISOU 656 CG2 THR A 96 4300 4244 4201 5 −6 0 A C SIGUIJ 656 CG2 THR A  96 1 0 0 220 117 290A C ATOM 657 C THR A  96 28.271 11.064 32.364 1.00 25.73 A C ANISOU 657C THR A  96 3284 4232 4245 −37 −73 −3 A C SIGUIJ 657 C THR A  96 1 0 0220 117 290 A C ATOM 658 O THR A  96 27.348 11.863 32.334 1.00 26.22 A OANISOU 658 O THR A  96 3374 4343 5847 63 −110 5 A O SIGUIJ 658 O THR A 96 1 0 0 221 55 289 A O ATOM 659 N GLN A  97 29.223 11.086 31.438 1.0025.95 A N ANISOU 659 N GLN A  97 3446 2803 4422 −4 98 0 A N SIGUIJ 659 NGLN A  97 1 0 0 221 62 289 A N ATOM 660 CA GLN A  97 29.316 12.20230.515 1.00 26.11 A C ANISOU 660 CA GLN A  97 4352 2818 4419 −155 4 5 AC SIGUIJ 660 CA GLN A  97 1 0 0 220 117 290 A C ATOM 661 CB GLN A  9730.759 12.402 30.099 1.00 26.98 A C ANISOU 661 CB GLN A  97 4370 37464402 −291 2 −12 A C SIGUIJ 661 CB GLN A  97 1 0 0 220 117 290 A C ATOM662 CG GLN A  97 30.868 13.209 28.809 1.00 28.30 A C ANISOU 662 CG GLN A 97 7564 3747 4466 113 518 18 A C SIGUIJ 662 CG GLN A  97 1 0 0 220 117290 A C ATOM 663 CD GLN A  97 32.287 13.304 28.275 1.00 28.85 A C ANISOU663 CD GLN A  97 7752 12170 5505 −481 913 −68 A C SIGUIJ 663 CD GLN A 97 1 0 0 220 117 290 A C ATOM 664 OE1 GLN A  97 33.062 12.322 28.3171.00 29.55 A O ANISOU 664 OE1 GLN A  97 7610 12063 21148 −623 173 18 A OSIGUIJ 664 OE1 GLN A  97 1 0 0 221 55 289 A O ATOM 665 NE2 GLN A  9732.643 14.484 27.760 1.00 29.45 A N ANISOU 665 NE2 GLN A  97 8173 122955335 −805 457 −5 A N SIGUIJ 665 NE2 GLN A  97 1 0 0 221 62 289 A N ATOM666 C GLN A  97 28.464 11.981 29.254 1.00 25.48 A C ANISOU 666 C GLN A 97 4377 3209 4425 −221 −1 −4 A C SIGUIJ 666 C GLN A  97 1 0 0 220 116290 A C ATOM 667 O GLN A  97 27.764 12.899 28.770 1.00 25.97 A O ANISOU667 O GLN A  97 4438 3244 4429 −178 0 −1 A O SIGUIJ 667 O GLN A  97 1 00 221 55 289 A O ATOM 668 N THR A  98 28.517 10.768 28.709 1.00 24.71 AN ANISOU 668 N THR A  98 2139 3129 4134 −535 501 154 A N SIGUIJ 668 NTHR A  98 1 0 0 221 62 289 A N ATOM 669 CA THR A  98 27.845 10.47427.448 1.00 23.55 A C ANISOU 669 CA THR A  98 2234 2397 4212 −131 363126 A C SIGUIJ 669 CA THR A  98 1 0 0 220 116 290 A C ATOM 670 CB THR A 98 28.672 9.553 26.535 1.00 24.14 A C ANISOU 670 CB THR A  98 2923 26524789 8 855 −11 A C SIGUIJ 670 CB THR A  98 1 0 0 220 116 290 A C ATOM671 OG1 THR A  98 28.693 8.242 27.090 1.00 25.41 A O ANISOU 671 OG1 THRA  98 2682 2630 4677 18 885 −60 A O SIGUIJ 671 OG1 THR A  98 1 0 0 22155 289 A O ATOM 672 CG2 THR A  98 30.139 10.013 26.443 1.00 24.07 A CANISOU 672 CG2 THR A  98 2936 2641 10007 22 1164 50 A C SIGUIJ 672 CG2THR A  98 1 0 0 220 116 290 A C ATOM 673 C THR A  98 26.474 9.803 27.6461.00 22.30 A C ANISOU 673 C THR A  98 2155 2072 2681 3 206 9 A C SIGUIJ673 C THR A  98 1 0 0 220 116 290 A C ATOM 674 O THR A  98 25.704 9.65526.689 1.00 22.13 A O ANISOU 674 O THR A  98 2401 3340 2810 −247 48 20 AO SIGUIJ 674 O THR A  98 1 0 0 221 55 289 A O ATOM 675 N HIS A  9926.193 9.360 28.868 1.00 20.81 A N ANISOU 675 N HIS A  99 1992 1996 26631 155 −3 A N SIGUIJ 675 N HIS A  99 1 0 0 221 62 289 A N ATOM 676 CA HISA  99 24.951 8.634 29.168 1.00 19.34 A C ANISOU 676 CA HIS A  99 19831987 2190 −2 56 0 A C SIGUIJ 676 CA HIS A  99 1 0 0 220 116 290 A C ATOM677 CB HIS A  99 23.715 9.438 28.729 1.00 19.79 A C ANISOU 677 CB HIS A 99 2185 2005 3747 4 −484 19 A C SIGUIJ 677 CB HIS A  99 1 0 0 220 115290 A C ATOM 678 CG HIS A  99 23.728 10.846 29.213 1.00 20.14 A C ANISOU678 CG HIS A  99 2351 2015 3830 −96 −197 −2 A C SIGUIJ 678 CG HIS A  991 0 0 220 115 290 A C ATOM 679 CD2 HIS A  99 24.036 11.996 28.581 1.0020.41 A C ANISOU 679 CD2 HIS A  99 2203 2017 3899 −57 −203 33 A C SIGUIJ679 CD2 HIS A  99 1 0 0 220 115 290 A C ATOM 680 ND1 HIS A  99 23.38211.190 30.501 1.00 20.50 A N ANISOU 680 ND1 HIS A  99 2303 1993 3822 −68−213 25 A N SIGUIJ 680 ND1 HIS A  99 1 0 0 221 62 289 A N ATOM 681 CE1HIS A  99 23.466 12.501 30.641 1.00 20.81 A C ANISOU 681 CE1 HIS A  993146 2005 4017 −152 95 −5 A C SIGUIJ 681 CE1 HIS A  99 1 0 0 220 115 290A C ATOM 682 NE2 HIS A  99 23.862 13.012 29.487 1.00 20.46 A N ANISOU682 NE2 HIS A  99 2633 2027 3964 −118 −62 3 A N SIGUIJ 682 NE2 HIS A  991 0 0 221 62 289 A N ATOM 683 C HIS A  99 24.866 7.234 28.583 1.00 18.13A C ANISOU 683 C HIS A  99 1816 1980 2160 34 45 −7 A C SIGUIJ 683 C HISA  99 1 0 0 220 115 290 A C ATOM 684 O HIS A  99 23.823 6.602 28.6851.00 17.56 A O ANISOU 684 O HIS A  99 1823 2014 1995 16 39 −3 A O SIGUIJ684 O HIS A  99 1 0 0 221 55 289 A O ATOM 685 N VAL A 100 25.945 6.72327.986 1.00 16.94 A N ANISOU 685 N VAL A 100 1769 1861 2023 −14 −8 −1 AN SIGUIJ 685 N VAL A 100 1 0 0 221 62 289 A N ATOM 686 CA VAL A 10025.868 5.369 27.479 1.00 15.87 A C ANISOU 686 CA VAL A 100 2252 18501935 −47 6 −1 A C SIGUIJ 686 CA VAL A 100 1 0 0 220 115 290 A C ATOM 687CB VAL A 100 27.067 5.027 26.514 1.00 16.42 A C ANISOU 687 CB VAL A 1002363 2101 2040 27 102 9 A C SIGUIJ 687 CB VAL A 100 1 0 0 220 114 290 AC ATOM 688 CG1 VAL A 100 27.048 5.936 25.329 1.00 17.26 A C ANISOU 688CG1 VAL A 100 5438 3054 2562 1740 1368 709 A C SIGUIJ 688 CG1 VAL A 1001 0 0 220 114 290 A C ATOM 689 CG2 VAL A 100 28.328 5.041 27.227 1.0017.69 A C ANISOU 689 CG2 VAL A 100 2424 2757 2236 10 −1 0 A C SIGUIJ 689CG2 VAL A 100 1 0 0 220 114 290 A C ATOM 690 C VAL A 100 25.769 4.38028.619 1.00 14.72 A C ANISOU 690 C VAL A 100 1790 1813 1929 −4 3 0 A CSIGUIJ 690 C VAL A 100 1 0 0 220 114 290 A C ATOM 691 O VAL A 100 26.2434.597 29.731 1.00 13.86 A O ANISOU 691 O VAL A 100 1438 1838 1841 −123192 52 A O SIGUIJ 691 O VAL A 100 1 0 0 221 55 289 A O ATOM 692 N ASN A101 25.088 3.291 28.328 1.00 14.10 A N ANISOU 692 N ASN A 101 1521 17581671 104 276 −91 A N SIGUIJ 692 N ASN A 101 1 0 0 221 62 289 A N ATOM693 CA ASN A 101 24.902 2.223 29.310 1.00 13.56 A C ANISOU 693 CA ASN A101 1559 1763 1689 87 245 −77 A C SIGUIJ 693 CA ASN A 101 1 0 0 220 114290 A C ATOM 694 CB ASN A 101 26.234 1.525 29.592 1.00 14.79 A C ANISOU694 CB ASN A 101 1609 1960 2094 186 184 −71 A C SIGUIJ 694 CB ASN A 1011 0 0 220 114 290 A C ATOM 695 CG ASN A 101 26.820 0.963 28.306 1.0015.68 A C ANISOU 695 CG ASN A 101 1696 2225 2125 340 181 −106 A C SIGUIJ695 CG ASN A 101 1 0 0 220 113 290 A C ATOM 696 OD1 ASN A 101 26.1000.323 27.515 1.00 16.85 A O ANISOU 696 OD1 ASN A 101 1850 2274 2189 254114 −66 A O SIGUIJ 696 OD1 ASN A 101 1 0 0 221 55 289 A O ATOM 697 ND2ASN A 101 28.091 1.260 28.064 1.00 17.12 A N ANISOU 697 ND2 ASN A 1011754 3141 2634 138 263 −32 A N SIGUIJ 697 ND2 ASN A 101 1 0 0 221 62 289A N ATOM 698 C ASN A 101 24.208 2.657 30.602 1.00 12.67 A C ANISOU 698 CASN A 101 1176 1390 1549 −9 34 1 A C SIGUIJ 698 C ASN A 101 1 0 0 220113 290 A C ATOM 699 O ASN A 101 24.582 2.223 31.707 1.00 12.12 A OANISOU 699 O ASN A 101 1255 1474 1494 236 113 −82 A O SIGUIJ 699 O ASN A101 1 0 0 221 55 289 A O ATOM 700 N ASP A 102 23.206 3.509 30.439 1.0011.51 A N ANISOU 700 N ASP A 102 1197 1369 1286 −5 3 0 A N SIGUIJ 700 NASP A 102 1 0 0 221 62 289 A N ATOM 701 CA ASP A 102 22.522 4.095 31.5891.00 11.50 A C ANISOU 701 CA ASP A 102 1226 1317 1276 −19 0 0 A C SIGUIJ701 CA ASP A 102 1 0 0 220 113 290 A C ATOM 702 CB ASP A 102 21.9245.449 31.192 1.00 11.19 A C ANISOU 702 CB ASP A 102 1327 1329 1286 0 −10 A C SIGUIJ 702 CB ASP A 102 1 0 0 220 113 290 A C ATOM 703 CG ASP A102 21.442 6.269 32.400 1.00 11.45 A C ANISOU 703 CG ASP A 102 1369 13441283 0 −2 0 A C SIGUIJ 703 CG ASP A 102 1 0 0 220 113 290 A C ATOM 704OD1 ASP A 102 21.673 5.856 33.563 1.00 11.51 A O ANISOU 704 OD1 ASP A102 1251 1347 1283 −10 2 0 A O SIGUIJ 704 OD1 ASP A 102 1 0 0 221 55 289A O ATOM 705 OD2 ASP A 102 20.801 7.313 32.169 1.00 11.08 A O ANISOU 705OD2 ASP A 102 1421 1354 1220 9 8 1 A O SIGUIJ 705 OD2 ASP A 102 1 0 0221 55 289 A O ATOM 706 C ASP A 102 21.455 3.144 32.131 1.00 11.59 A CANISOU 706 C ASP A 102 1223 1280 1252 2 0 0 A C SIGUIJ 706 C ASP A 102 10 0 220 113 290 A C ATOM 707 O ASP A 102 20.245 3.459 32.084 1.00 12.68A O ANISOU 707 O ASP A 102 1258 1687 1990 120 −29 6 A O SIGUIJ 707 O ASPA 102 1 0 0 221 55 289 A O ATOM 708 N LEU A 103 21.891 2.007 32.676 1.0011.50 A N ANISOU 708 N LEU A 103 1270 1269 1266 0 0 0 A N SIGUIJ 708 NLEU A 103 1 0 0 221 62 289 A N ATOM 709 CA LEU A 103 20.952 1.083 33.2861.00 11.53 A C ANISOU 709 CA LEU A 103 1278 1263 1325 3 4 0 A C SIGUIJ709 CA LEU A 103 1 0 0 220 112 290 A C ATOM 710 CB LEU A 103 20.3280.088 32.300 1.00 13.13 A C ANISOU 710 CB LEU A 103 1965 1515 1359 −384−11 7 A C SIGUIJ 710 CB LEU A 103 1 0 0 220 112 290 A C ATOM 711 CG LEUA 103 21.231 −1.005 31.756 1.00 13.55 A C ANISOU 711 CG LEU A 103 23121741 1668 −140 116 −26 A C SIGUIJ 711 CG LEU A 103 1 0 0 220 112 290 A CATOM 712 CD1 LEU A 103 20.335 −2.057 30.957 1.00 14.38 A C ANISOU 712CD1 LEU A 103 2180 1679 1605 −68 167 −20 A C SIGUIJ 712 CD1 LEU A 103 10 0 220 112 290 A C ATOM 713 CD2 LEU A 103 22.241 −0.489 30.744 1.0014.48 A C ANISOU 713 CD2 LEU A 103 2282 1609 1715 −26 149 −6 A C SIGUIJ713 CD2 LEU A 103 1 0 0 220 112 290 A C ATOM 714 C LEU A 103 21.5630.405 34.495 1.00 10.75 A C ANISOU 714 C LEU A 103 1217 1210 1320 −1 9−1 A C SIGUIJ 714 C LEU A 103 1 0 0 220 112 290 A C ATOM 715 O LEU A 10322.807 0.317 34.647 1.00 10.74 A O ANISOU 715 O LEU A 103 1212 1289 14645 0 0 A O SIGUIJ 715 O LEU A 103 1 0 0 221 55 289 A O ATOM 716 N MET A104 20.688 −0.027 35.400 1.00 10.28 A N ANISOU 716 N MET A 104 1183 10621306 86 12 −3 A N SIGUIJ 716 N MET A 104 1 0 0 221 62 289 A N ATOM 717CA MET A 104 21.074 −0.508 36.711 1.00 9.73 A C ANISOU 717 CA MET A 1041188 1015 1310 2 −12 0 A C SIGUIJ 717 CA MET A 104 1 0 0 220 112 290 A CATOM 718 CB MET A 104 21.242 0.689 37.670 1.00 9.60 A C ANISOU 718 CBMET A 104 1156 1018 1297 −47 20 0 A C SIGUIJ 718 CB MET A 104 1 0 0 220111 290 A C ATOM 719 CG MET A 104 21.621 0.322 39.100 1.00 9.22 A CANISOU 719 CG MET A 104 1309 1117 1294 25 1 0 A C SIGUIJ 719 CG MET A104 1 0 0 220 111 290 A C ATOM 720 SD MET A 104 21.934 1.769 40.144 1.0010.10 A S ANISOU 720 SD MET A 104 1365 1162 1408 92 −113 −79 A S SIGUIJ720 SD MET A 104 1 0 0 221 48 289 A S ATOM 721 CE MET A 104 20.275 2.46140.318 1.00 9.48 A C ANISOU 721 CE MET A 104 1365 1153 1527 95 −27 5 A CSIGUIJ 721 CE MET A 104 1 0 0 220 111 290 A C ATOM 722 C MET A 10419.992 −1.444 37.231 1.00 9.69 A C ANISOU 722 C MET A 104 1168 965 135960 28 −1 A C SIGUIJ 722 C MET A 104 1 0 0 220 111 290 A C ATOM 723 O META 104 18.798 −1.172 37.066 1.00 10.37 A O ANISOU 723 O MET A 104 11841080 1646 87 4 1 A O SIGUIJ 723 O MET A 104 1 0 0 221 55 289 A O ATOM724 N LEU A 105 20.411 −2.514 37.907 1.00 9.28 A N ANISOU 724 N LEU A105 1116 966 1347 39 1 0 A N SIGUIJ 724 N LEU A 105 1 0 0 221 62 289 A NATOM 725 CA LEU A 105 19.499 −3.414 38.580 1.00 9.44 A C ANISOU 725 CALEU A 105 1032 926 1390 124 14 1 A C SIGUIJ 725 CA LEU A 105 1 0 0 220111 290 A C ATOM 726 CB LEU A 105 19.892 −4.877 38.263 1.00 10.10 A CANISOU 726 CB LEU A 105 1389 953 1640 202 53 −30 A C SIGUIJ 726 CB LEU A105 1 0 0 220 111 290 A C ATOM 727 CG LEU A 105 19.402 −5.290 36.8911.00 10.37 A C ANISOU 727 CG LEU A 105 1620 1043 1658 20 −1 0 A C SIGUIJ727 CG LEU A 105 1 0 0 220 110 290 A C ATOM 728 CD1 LEU A 105 20.243−6.494 36.416 1.00 11.78 A C ANISOU 728 CD1 LEU A 105 2116 1331 1753 403−62 −49 A C SIGUIJ 728 CD1 LEU A 105 1 0 0 220 110 290 A C ATOM 729 CD2LEU A 105 17.882 −5.623 36.914 1.00 11.41 A C ANISOU 729 CD2 LEU A 1051642 1495 1676 −87 0 −1 A C SIGUIJ 729 CD2 LEU A 105 1 0 0 220 110 290 AC ATOM 730 C LEU A 105 19.553 −3.168 40.074 1.00 9.78 A C ANISOU 730 CLEU A 105 1222 1045 1390 44 19 −1 A C SIGUIJ 730 C LEU A 105 1 0 0 220110 290 A C ATOM 731 O LEU A 105 20.639 −3.056 40.668 1.00 10.06 A OANISOU 731 O LEU A 105 1251 1567 1485 −8 −34 −1 A O SIGUIJ 731 O LEU A105 1 0 0 221 55 289 A O ATOM 732 N VAL A 106 18.376 −3.053 40.700 1.009.72 A N ANISOU 732 N VAL A 106 1211 1073 1326 60 −6 1 A N SIGUIJ 732 NVAL A 106 1 0 0 221 62 289 A N ATOM 733 CA VAL A 106 18.253 −2.80642.118 1.00 9.98 A C ANISOU 733 CA VAL A 106 1165 997 1333 −15 −2 0 A CSIGUIJ 733 CA VAL A 106 1 0 0 220 110 290 A C ATOM 734 CB VAL A 10617.319 −1.592 42.401 1.00 9.38 A C ANISOU 734 CB VAL A 106 1195 10271322 18 −11 0 A C SIGUIJ 734 CB VAL A 106 1 0 0 220 110 290 A C ATOM 735CG1 VAL A 106 17.014 −1.470 43.855 1.00 10.46 A C ANISOU 735 CG1 VAL A106 1714 1079 1335 127 79 19 A C SIGUIJ 735 CG1 VAL A 106 1 0 0 220 110290 A C ATOM 736 CG2 VAL A 106 17.961 −0.326 41.839 1.00 10.19 A CANISOU 736 CG2 VAL A 106 1372 1081 1382 −80 0 3 A C SIGUIJ 736 CG2 VAL A106 1 0 0 220 109 290 A C ATOM 737 C VAL A 106 17.652 −4.046 42.767 1.009.99 A C ANISOU 737 C VAL A 106 1187 973 1384 17 69 0 A C SIGUIJ 737 CVAL A 106 1 0 0 220 109 290 A C ATOM 738 O VAL A 106 16.621 −4.55842.315 1.00 10.40 A O ANISOU 738 O VAL A 106 1257 1052 1559 −27 −37 2 AO SIGUIJ 738 O VAL A 106 1 0 0 221 55 289 A O ATOM 739 N LYS A 10718.348 −4.591 43.770 1.00 10.39 A N ANISOU 739 N LYS A 107 1370 10191447 76 −6 3 A N SIGUIJ 739 N LYS A 107 1 0 0 221 62 289 A N ATOM 740 CALYS A 107 17.914 −5.842 44.388 1.00 10.98 A C ANISOU 740 CA LYS A 1071397 1005 1459 101 3 −2 A C SIGUIJ 740 CA LYS A 107 1 0 0 220 109 290 AC ATOM 741 CB LYS A 107 19.106 −6.668 44.803 1.00 11.90 A C ANISOU 741CB LYS A 107 1601 1250 1934 297 −164 11 A C SIGUIJ 741 CB LYS A 107 1 00 220 109 290 A C ATOM 742 CG LYS A 107 18.732 −8.049 45.245 1.00 13.32A C ANISOU 742 CG LYS A 107 1830 1239 2066 316 18 −9 A C SIGUIJ 742 CGLYS A 107 1 0 0 220 109 290 A C ATOM 743 CD LYS A 107 19.993 −8.86345.608 1.00 14.98 A C ANISOU 743 CD LYS A 107 2079 1905 2194 715 85 171A C SIGUIJ 743 CD LYS A 107 1 0 0 220 109 290 A C ATOM 744 CE LYS A 10719.721 −10.362 45.772 1.00 16.42 A C ANISOU 744 CE LYS A 107 2713 19213605 647 435 263 A C SIGUIJ 744 CE LYS A 107 1 0 0 220 109 290 A C ATOM745 NZ LYS A 107 21.008 −11.032 46.297 1.00 17.72 A N ANISOU 745 NZ LYSA 107 3026 2306 4028 981 93 −57 A N SIGUIJ 745 NZ LYS A 107 1 0 0 221 62289 A N ATOM 746 C LYS A 107 17.065 −5.531 45.604 1.00 11.00 A C ANISOU746 C LYS A 107 1395 1032 1450 71 −1 1 A C SIGUIJ 746 C LYS A 107 1 0 0220 108 290 A C ATOM 747 O LYS A 107 17.547 −4.887 46.553 1.00 11.19 A OANISOU 747 O LYS A 107 1567 1170 1442 −78 5 −2 A O SIGUIJ 747 O LYS A107 1 0 0 221 55 289 A O ATOM 748 N LEU A 108 15.802 −5.981 45.603 1.0011.24 A N ANISOU 748 N LEU A 108 1422 1231 1342 2 0 0 A N SIGUIJ 748 NLEU A 108 1 0 0 221 62 289 A N ATOM 749 CA LEU A 108 14.907 −5.71146.740 1.00 11.85 A C ANISOU 749 CA LEU A 108 1465 1277 1352 9 22 1 A CSIGUIJ 749 CA LEU A 108 1 0 0 220 108 290 A C ATOM 750 CB LEU A 10813.474 −6.132 46.387 1.00 12.01 A C ANISOU 750 CB LEU A 108 1478 13431502 −20 −1 0 A C SIGUIJ 750 CB LEU A 108 1 0 0 220 108 290 A C ATOM 751CG LEU A 108 12.919 −5.418 45.167 1.00 11.86 A C ANISOU 751 CG LEU A 1081536 1382 1505 24 −4 −2 A C SIGUIJ 751 CG LEU A 108 1 0 0 220 108 290 AC ATOM 752 CD1 LEU A 108 11.513 −5.984 44.837 1.00 12.58 A C ANISOU 752CD1 LEU A 108 1614 1501 2352 −35 −229 51 A C SIGUIJ 752 CD1 LEU A 108 10 0 220 108 290 A C ATOM 753 CD2 LEU A 108 12.846 −3.926 45.399 1.0012.88 A C ANISOU 753 CD2 LEU A 108 2113 1389 1608 57 −30 −3 A C SIGUIJ753 CD2 LEU A 108 1 0 0 220 108 290 A C ATOM 754 C LEU A 108 15.392−6.546 47.952 1.00 12.20 A C ANISOU 754 C LEU A 108 1519 1267 1374 −32−25 5 A C SIGUIJ 754 C LEU A 108 1 0 0 220 108 290 A C ATOM 755 O LEU A108 15.854 −7.685 47.786 1.00 12.60 A O ANISOU 755 O LEU A 108 1852 13131599 91 70 18 A O SIGUIJ 755 O LEU A 108 1 0 0 221 55 289 A O ATOM 756 NASN A 109 15.259 −6.006 49.139 1.00 12.92 A N ANISOU 756 N ASN A 1091573 1345 1374 −40 −4 1 A N SIGUIJ 756 N ASN A 109 1 0 0 221 62 289 A NATOM 757 CA ASN A 109 15.681 −6.757 50.345 1.00 13.41 A C ANISOU 757 CAASN A 109 1847 1426 1378 46 −54 −5 A C SIGUIJ 757 CA ASN A 109 1 0 0 220107 290 A C ATOM 758 CB ASN A 109 15.811 −5.836 51.542 1.00 13.05 A CANISOU 758 CB ASN A 109 1687 1456 1376 40 −37 −5 A C SIGUIJ 758 CB ASN A109 1 0 0 220 107 290 A C ATOM 759 CG ASN A 109 17.005 −4.891 51.4311.00 12.98 A C ANISOU 759 CG ASN A 109 1680 1476 1525 43 −12 −3 A CSIGUIJ 759 CG ASN A 109 1 0 0 220 107 290 A C ATOM 760 OD1 ASN A 10917.785 −4.886 50.442 1.00 12.94 A O ANISOU 760 OD1 ASN A 109 1730 15651552 32 28 5 A O SIGUIJ 760 OD1 ASN A 109 1 0 0 221 55 289 A O ATOM 761ND2 ASN A 109 17.173 −4.096 52.470 1.00 13.30 A N ANISOU 761 ND2 ASN A109 1687 1502 1533 28 −5 −1 A N SIGUIJ 761 ND2 ASN A 109 1 0 0 221 61289 A N ATOM 762 C ASN A 109 14.724 −7.859 50.719 1.00 14.69 A C ANISOU762 C ASN A 109 2099 1588 1559 −140 26 −7 A C SIGUIJ 762 C ASN A 109 1 00 220 107 290 A C ATOM 763 O ASN A 109 15.098 −8.816 51.433 1.00 14.91 AO ANISOU 763 O ASN A 109 2374 1641 1909 −293 −314 134 A O SIGUIJ 763 OASN A 109 1 0 0 221 55 289 A O ATOM 764 N ASER A 110 13.476 −7.73650.267 0.50 15.29 A N ANISOU 764 N ASER A 110 2135 1762 1816 −127 −63 22A N SIGUIJ 764 N ASER A 110 1 0 0 221 61 289 A N ATOM 765 N BSER A 11013.510 −7.789 50.203 0.50 17.48 A N ANISOU 765 N BSER A 110 2143 16401822 −165 −84 33 A N SIGUIJ 765 N BSER A 110 1 0 0 221 61 289 A N ATOM766 CA ASER A 110 12.395 −8.696 50.529 0.50 16.79 A C ANISOU 766 CA ASERA 110 2341 2020 1933 −347 −38 28 A C SIGUIJ 766 CA ASER A 110 1 0 0 220107 290 A C ATOM 767 CA BSER A 110 12.531 −8.835 50.409 0.50 18.98 A CANISOU 767 CA BSER A 110 2251 1710 2035 −244 −20 14 A C SIGUIJ 767 CABSER A 110 1 0 0 220 107 290 A C ATOM 768 CB ASER A 110 11.484 −8.21051.703 0.50 17.69 A C ANISOU 768 CB ASER A 110 2668 2689 2019 −1 64 1 AC SIGUIJ 768 CB ASER A 110 1 0 0 220 107 290 A C ATOM 769 CB BSER A 11011.640 −8.504 51.614 0.50 19.88 A C ANISOU 769 CB BSER A 110 2409 24292071 2 24 −1 A C SIGUIJ 769 CB BSER A 110 1 0 0 220 107 290 A C ATOM 770OG ASER A 110 10.860 −6.950 51.498 0.50 19.99 A O ANISOU 770 OG ASER A110 2698 2686 2036 1 23 1 A O SIGUIJ 770 OG ASER A 110 1 0 0 221 55 289A O ATOM 771 OG BSER A 110 12.411 −8.427 52.800 0.50 22.18 A O ANISOU771 OG BSER A 110 2462 2576 2090 −34 −7 −1 A O SIGUIJ 771 OG BSER A 1101 0 0 221 55 289 A O ATOM 772 C ASER A 110 11.603 −8.807 49.216 0.5017.01 A C ANISOU 772 C ASER A 110 2432 1844 1956 −290 −74 37 A C SIGUIJ772 C ASER A 110 1 0 0 220 106 290 A C ATOM 773 C BSER A 110 11.713−8.885 49.138 0.50 19.20 A C ANISOU 773 C BSER A 110 2224 1826 2022 −206−2 1 A C SIGUIJ 773 C BSER A 110 1 0 0 220 106 290 A C ATOM 774 O ASER A110 11.619 −7.866 48.392 0.50 16.63 A O ANISOU 774 O ASER A 110 14391829 1952 −117 96 24 A O SIGUIJ 774 O ASER A 110 1 0 0 221 55 289 A OATOM 775 O BSER A 110 11.771 −7.974 48.291 0.50 18.82 A O ANISOU 775 OBSER A 110 2693 1817 2024 −219 −7 2 A O SIGUIJ 775 O BSER A 110 1 0 0221 55 289 A O ATOM 776 N GLN A 111 10.933 −9.932 48.996 1.00 17.12 A NANISOU 776 N GLN A 111 1988 1698 1958 −28 0 0 A N SIGUIJ 776 N GLN A 1111 0 0 221 61 289 A N ATOM 777 CA GLN A 111 10.229 −10.117 47.737 1.0018.12 A C ANISOU 777 CA GLN A 111 2166 1970 1991 −137 −72 43 A C SIGUIJ777 CA GLN A 111 1 0 0 220 106 290 A C ATOM 778 CB GLN A 111 9.766−11.557 47.579 1.00 19.48 A C ANISOU 778 CB GLN A 111 2371 1998 2746−187 −160 −30 A C SIGUIJ 778 CB GLN A 111 1 0 0 220 106 290 A C ATOM 779CG GLN A 111 10.845 −12.568 47.392 1.00 22.14 A C ANISOU 779 CG GLN A111 2793 2264 7919 80 852 92 A C SIGUIJ 779 CG GLN A 111 1 0 0 220 106290 A C ATOM 780 CD GLN A 111 10.308 −13.819 46.758 1.00 23.28 A CANISOU 780 CD GLN A 111 6731 2748 9230 −935 −488 −3 A C SIGUIJ 780 CDGLN A 111 1 0 0 220 106 290 A C ATOM 781 OE1 GLN A 111 10.959 −14.43445.907 1.00 24.92 A O ANISOU 781 OE1 GLN A 111 9238 4863 9655 1005 29−45 A O SIGUIJ 781 OE1 GLN A 111 1 0 0 221 55 289 A O ATOM 782 NE2 GLN A111 9.103 −14.201 47.157 1.00 24.43 A N ANISOU 782 NE2 GLN A 111 67652621 9593 −908 −357 −33 A N SIGUIJ 782 NE2 GLN A 111 1 0 0 221 61 289 AN ATOM 783 C GLN A 111 9.019 −9.201 47.593 1.00 17.61 A C ANISOU 783 CGLN A 111 2163 1938 1772 −146 −57 24 A C SIGUIJ 783 C GLN A 111 1 0 0220 106 290 A C ATOM 784 O GLN A 111 8.280 −8.956 48.526 1.00 18.10 A OANISOU 784 O GLN A 111 2463 2452 1934 2 144 9 A O SIGUIJ 784 O GLN A 1111 0 0 221 55 289 A O ATOM 785 N ALA A 112 8.811 −8.718 46.377 1.00 17.05A N ANISOU 785 N ALA A 112 2003 1853 1753 −48 14 −4 A N SIGUIJ 785 N ALAA 112 1 0 0 221 61 289 A N ATOM 786 CA ALA A 112 7.570 −8.041 46.0571.00 16.69 A C ANISOU 786 CA ALA A 112 1968 1731 1752 −118 9 −4 A CSIGUIJ 786 CA ALA A 112 1 0 0 220 106 290 A C ATOM 787 CB ALA A 1127.670 −7.434 44.679 1.00 16.65 A C ANISOU 787 CB ALA A 112 2000 17441751 −188 −5 3 A C SIGUIJ 787 CB ALA A 112 1 0 0 220 105 290 A C ATOM788 C ALA A 112 6.462 −9.070 46.059 1.00 16.29 A C ANISOU 788 C ALA A112 1843 1588 2130 17 8 0 A C SIGUIJ 788 C ALA A 112 1 0 0 220 105 290 AC ATOM 789 O ALA A 112 6.640 −10.181 45.548 1.00 16.84 A O ANISOU 789 OALA A 112 1983 1611 2562 −162 436 −121 A O SIGUIJ 789 O ALA A 112 1 0 0221 55 289 A O ATOM 790 N ARG A 113 5.317 −8.648 46.555 1.00 15.89 A NANISOU 790 N ARG A 113 1770 1310 2014 −103 −46 3 A N SIGUIJ 790 N ARG A113 1 0 0 221 61 289 A N ATOM 791 CA ARG A 113 4.134 −9.498 46.561 1.0016.10 A C ANISOU 791 CA ARG A 113 1809 1395 2123 −170 −36 −3 A C SIGUIJ791 CA ARG A 113 1 0 0 220 105 290 A C ATOM 792 CB ARG A 113 3.307−9.105 47.789 1.00 16.85 A C ANISOU 792 CB ARG A 113 1921 1804 2139 10−9 0 A C SIGUIJ 792 CB ARG A 113 1 0 0 220 105 290 A C ATOM 793 CG ARG A113 2.029 −9.912 47.973 1.00 18.15 A C ANISOU 793 CG ARG A 113 2179 24622531 −397 25 63 A C SIGUIJ 793 CG ARG A 113 1 0 0 220 105 290 A C ATOM794 CD ARG A 113 1.363 −9.577 49.279 1.00 19.35 A C ANISOU 794 CD ARG A113 2480 3481 2568 4 76 9 A C SIGUIJ 794 CD ARG A 113 1 0 0 220 105 290A C ATOM 795 NE ARG A 113 0.698 −8.280 49.188 1.00 21.35 A N ANISOU 795NE ARG A 113 3765 3821 3177 658 33 35 A N SIGUIJ 795 NE ARG A 113 1 0 0221 61 289 A N ATOM 796 CZ ARG A 113 1.124 −7.145 49.720 1.00 21.76 A CANISOU 796 CZ ARG A 113 4752 4010 2907 147 339 40 A C SIGUIJ 796 CZ ARGA 113 1 0 0 220 105 290 A C ATOM 797 NH1 ARG A 113 2.263 −7.116 50.4031.00 22.87 A N ANISOU 797 NH1 ARG A 113 4831 9256 3113 35 215 4 A NSIGUIJ 797 NH1 ARG A 113 1 0 0 221 61 289 A N ATOM 798 NH2 ARG A 1130.407 −6.033 49.560 1.00 22.28 A N ANISOU 798 NH2 ARG A 113 4317 38192073 −127 387 −52 A N SIGUIJ 798 NH2 ARG A 113 1 0 0 221 61 289 A N ATOM799 C ARG A 113 3.379 −9.243 45.280 1.00 16.20 A C ANISOU 799 C ARG A113 1605 1249 2069 −215 83 13 A C SIGUIJ 799 C ARG A 113 1 0 0 220 104290 A C ATOM 800 O ARG A 113 2.898 −8.126 45.043 1.00 15.52 A O ANISOU800 O ARG A 113 1821 1271 2200 −140 −20 −2 A O SIGUIJ 800 O ARG A 113 10 0 221 55 289 A O ATOM 801 N LEU A 114 3.248 −10.255 44.430 1.00 16.44A N ANISOU 801 N LEU A 114 1747 1247 2127 −113 −55 1 A N SIGUIJ 801 NLEU A 114 1 0 0 221 61 289 A N ATOM 802 CA LEU A 114 2.613 −10.09543.145 1.00 17.11 A C ANISOU 802 CA LEU A 114 1733 1504 2137 −27 −60 −2A C SIGUIJ 802 CA LEU A 114 1 0 0 220 104 290 A C ATOM 803 CB LEU A 1143.090 −11.177 42.160 1.00 16.77 A C ANISOU 803 CB LEU A 114 1677 15002110 −15 −116 2 A C SIGUIJ 803 CB LEU A 114 1 0 0 220 104 290 A C ATOM804 CG LEU A 114 4.604 −11.244 41.936 1.00 16.57 A C ANISOU 804 CG LEU A114 1686 1414 2554 −26 −58 2 A C SIGUIJ 804 CG LEU A 114 1 0 0 220 104290 A C ATOM 805 CD1 LEU A 114 4.934 −12.344 40.931 1.00 16.95 A CANISOU 805 CD1 LEU A 114 2302 1465 2569 124 −15 2 A C SIGUIJ 805 CD1 LEUA 114 1 0 0 220 104 290 A C ATOM 806 CD2 LEU A 114 5.114 −9.909 41.4321.00 17.11 A C ANISOU 806 CD2 LEU A 114 2276 1462 3081 −108 329 44 A CSIGUIJ 806 CD2 LEU A 114 1 0 0 220 104 290 A C ATOM 807 C LEU A 1141.097 −10.149 43.285 1.00 18.00 A C ANISOU 807 C LEU A 114 1728 15732995 −6 15 0 A C SIGUIJ 807 C LEU A 114 1 0 0 220 104 290 A C ATOM 808 OLEU A 114 0.577 −10.827 44.215 1.00 18.24 A O ANISOU 808 O LEU A 1142536 1872 3167 −325 254 55 A O SIGUIJ 808 O LEU A 114 1 0 0 221 55 289 AO ATOM 809 N SER A 115 0.408 −9.482 42.337 1.00 18.77 A N ANISOU 809 NSER A 115 1763 1552 3043 −36 −49 4 A N SIGUIJ 809 N SER A 115 1 0 0 22161 289 A N ATOM 810 CA SER A 115 −1.055 −9.364 42.358 1.00 19.64 A CANISOU 810 CA SER A 115 1766 2476 3337 46 −53 3 A C SIGUIJ 810 CA SER A115 1 0 0 220 104 290 A C ATOM 811 CB SER A 115 −1.452 −8.523 43.5391.00 20.16 A C ANISOU 811 CB SER A 115 2626 2474 3445 12 261 −3 A CSIGUIJ 811 CB SER A 115 1 0 0 220 104 290 A C ATOM 812 OG SER A 115−1.140 −7.162 43.223 1.00 21.32 A O ANISOU 812 OG SER A 115 3340 24984640 27 979 112 A O SIGUIJ 812 OG SER A 115 1 0 0 221 55 289 A O ATOM813 C SER A 115 −1.528 −8.645 41.083 1.00 19.90 A C ANISOU 813 C SER A115 1763 2272 3371 −161 −175 −32 A C SIGUIJ 813 C SER A 115 1 0 0 220103 290 A C ATOM 814 O SER A 115 −0.753 −8.325 40.227 1.00 20.05 A OANISOU 814 O SER A 115 1816 1909 3486 9 −71 3 A O SIGUIJ 814 O SER A 1151 0 0 221 54 289 A O ATOM 815 N SER A 116 −2.838 −8.428 40.931 1.0020.69 A N ANISOU 815 N SER A 116 1795 2418 5718 −141 −452 −36 A N SIGUIJ815 N SER A 116 1 0 0 221 61 289 A N ATOM 816 CA SER A 116 −3.329 −7.55739.857 1.00 20.69 A C ANISOU 816 CA SER A 116 1953 2455 5706 −48 −455−54 A C SIGUIJ 816 CA SER A 116 1 0 0 220 103 290 A C ATOM 817 CB SER A116 −4.865 −7.371 39.972 1.00 21.19 A C ANISOU 817 CB SER A 116 19863668 8877 97 −207 8 A C SIGUIJ 817 CB SER A 116 1 0 0 220 103 290 A CATOM 818 OG SER A 116 −5.215 −6.768 41.202 1.00 22.45 A O ANISOU 818 OGSER A 116 2138 3815 8778 623 −419 88 A O SIGUIJ 818 OG SER A 116 1 0 0221 54 289 A O ATOM 819 C SER A 116 −2.644 −6.171 39.784 1.00 20.42 A CANISOU 819 C SER A 116 2214 2521 4640 −172 −509 −96 A C SIGUIJ 819 C SERA 116 1 0 0 220 103 290 A C ATOM 820 O SER A 116 −2.550 −5.610 38.6971.00 21.05 A O ANISOU 820 O SER A 116 2131 2640 4675 −95 −490 −34 A OSIGUIJ 820 O SER A 116 1 0 0 221 54 289 A O ATOM 821 N MET A 117 −2.153−5.667 40.921 1.00 19.82 A N ANISOU 821 N MET A 117 1407 1770 4466 182−306 96 A N SIGUIJ 821 N MET A 117 1 0 0 221 61 289 A N ATOM 822 CA META 117 −1.520 −4.350 40.929 1.00 19.03 A C ANISOU 822 CA MET A 117 17291849 3850 32 −57 7 A C SIGUIJ 822 CA MET A 117 1 0 0 220 103 290 A CATOM 823 CB MET A 117 −1.943 −3.547 42.132 1.00 20.66 A C ANISOU 823 CBMET A 117 2266 1946 3895 138 61 7 A C SIGUIJ 823 CB MET A 117 1 0 0 220103 290 A C ATOM 824 CG MET A 117 −3.379 −2.897 41.980 1.00 22.36 A CANISOU 824 CG MET A 117 2554 3281 5392 737 −96 42 A C SIGUIJ 824 CG META 117 1 0 0 220 103 290 A C ATOM 825 SD MET A 117 −3.694 −2.019 40.3871.00 24.64 A S ANISOU 825 SD MET A 117 2679 3265 5461 451 −289 102 A SSIGUIJ 825 SD MET A 117 1 0 0 221 48 289 A S ATOM 826 CE MET A 117−3.179 −0.412 40.861 1.00 23.83 A C ANISOU 826 CE MET A 117 3978 34385677 −2 −189 3 A C SIGUIJ 826 CE MET A 117 1 0 0 220 103 290 A C ATOM827 C MET A 117 0.001 −4.376 40.899 1.00 17.74 A C ANISOU 827 C MET A117 1732 1355 2342 25 −74 1 A C SIGUIJ 827 C MET A 117 1 0 0 220 102 290A C ATOM 828 O MET A 117 0.612 −3.307 40.805 1.00 17.16 A O ANISOU 828 OMET A 117 1737 1336 2063 38 −73 −2 A O SIGUIJ 828 O MET A 117 1 0 0 22154 289 A O ATOM 829 N VAL A 118 0.611 −5.574 41.004 1.00 16.28 A NANISOU 829 N VAL A 118 1624 1330 2554 −26 −76 3 A N SIGUIJ 829 N VAL A118 1 0 0 221 61 289 A N ATOM 830 CA VAL A 118 2.095 −5.723 40.950 1.0015.27 A C ANISOU 830 CA VAL A 118 1629 1193 2104 −36 −94 1 A C SIGUIJ830 CA VAL A 118 1 0 0 220 102 290 A C ATOM 831 CB VAL A 118 2.649−5.931 42.377 1.00 14.08 A C ANISOU 831 CB VAL A 118 1405 1263 2061 3 120 A C SIGUIJ 831 CB VAL A 118 1 0 0 220 102 290 A C ATOM 832 CG1 VAL A118 4.176 −6.145 42.338 1.00 13.42 A C ANISOU 832 CG1 VAL A 118 14081247 2297 −1 22 0 A C SIGUIJ 832 CG1 VAL A 118 1 0 0 220 102 290 A CATOM 833 CG2 VAL A 118 2.304 −4.722 43.232 1.00 14.26 A C ANISOU 833 CG2VAL A 118 1562 1269 2099 11 76 1 A C SIGUIJ 833 CG2 VAL A 118 1 0 0 220102 290 A C ATOM 834 C VAL A 118 2.414 −6.890 40.055 1.00 15.11 A CANISOU 834 C VAL A 118 1434 1161 2121 −131 −60 1 A C SIGUIJ 834 C VAL A118 1 0 0 220 102 290 A C ATOM 835 O VAL A 118 2.127 −8.060 40.396 1.0014.71 A O ANISOU 835 O VAL A 118 1814 1179 2218 −232 −43 −2 A O SIGUIJ835 O VAL A 118 1 0 0 221 54 289 A O ATOM 836 N LYS A 119 2.949 −6.59338.882 1.00 15.20 A N ANISOU 836 N LYS A 119 1746 1300 2172 −183 63 7 AN SIGUIJ 836 N LYS A 119 1 0 0 221 61 289 A N ATOM 837 CA LYS A 1193.202 −7.592 37.838 1.00 15.90 A C ANISOU 837 CA LYS A 119 1689 13032175 −188 65 3 A C SIGUIJ 837 CA LYS A 119 1 0 0 220 102 290 A C ATOM838 CB LYS A 119 2.212 −7.325 36.693 1.00 17.02 A C ANISOU 838 CB LYS A119 2159 1934 2519 −57 −311 59 A C SIGUIJ 838 CB LYS A 119 1 0 0 220 102290 A C ATOM 839 CG LYS A 119 2.221 −8.230 35.431 1.00 18.86 A C ANISOU839 CG LYS A 119 2605 2223 2673 −541 42 −144 A C SIGUIJ 839 CG LYS A 1191 0 0 220 102 290 A C ATOM 840 CD LYS A 119 1.015 −7.886 34.493 1.0020.61 A C ANISOU 840 CD LYS A 119 2753 4116 2776 −120 4 9 A C SIGUIJ 840CD LYS A 119 1 0 0 220 101 290 A C ATOM 841 CE LYS A 119 1.219 −6.62533.566 1.00 21.72 A C ANISOU 841 CE LYS A 119 12388 4128 2918 −702 1335−104 A C SIGUIJ 841 CE LYS A 119 1 0 0 220 101 290 A C ATOM 842 NZ LYS A119 0.012 −6.188 32.720 1.00 22.83 A N ANISOU 842 NZ LYS A 119 150939430 6830 1341 −1471 −282 A N SIGUIJ 842 NZ LYS A 119 1 0 0 221 61 289 AN ATOM 843 C LYS A 119 4.607 −7.439 37.305 1.00 15.59 A C ANISOU 843 CLYS A 119 1648 1253 1821 −207 −51 −38 A C SIGUIJ 843 C LYS A 119 1 0 0220 101 290 A C ATOM 844 O LYS A 119 5.169 −6.306 37.257 1.00 15.70 A OANISOU 844 O LYS A 119 1822 1301 2500 −310 −73 −4 A O SIGUIJ 844 O LYS A119 1 0 0 221 54 289 A O ATOM 845 N LYS A 120 5.202 −8.532 36.877 1.0014.95 A N ANISOU 845 N LYS A 120 1615 1235 1756 −241 −16 −21 A N SIGUIJ845 N LYS A 120 1 0 0 221 61 289 A N ATOM 846 CA LYS A 120 6.481 −8.48236.187 1.00 15.06 A C ANISOU 846 CA LYS A 120 1640 1387 1823 −226 23 20A C SIGUIJ 846 CA LYS A 120 1 0 0 220 101 290 A C ATOM 847 CB LYS A 1207.023 −9.919 36.034 1.00 15.87 A C ANISOU 847 CB LYS A 120 2003 14502116 −80 13 −2 A C SIGUIJ 847 CB LYS A 120 1 0 0 220 101 290 A C ATOM848 CG LYS A 120 7.214 −10.634 37.396 1.00 17.11 A C ANISOU 848 CG LYS A120 2185 1579 2148 −69 −15 47 A C SIGUIJ 848 CG LYS A 120 1 0 0 220 101290 A C ATOM 849 CD LYS A 120 7.903 −12.032 37.231 1.00 19.27 A C ANISOU849 CD LYS A 120 2483 1637 3342 40 265 32 A C SIGUIJ 849 CD LYS A 120 10 0 220 101 290 A C ATOM 850 CE LYS A 120 7.005 −13.100 36.616 1.0020.80 A C ANISOU 850 CE LYS A 120 3181 2025 3841 −384 −22 −5 A C SIGUIJ850 CE LYS A 120 1 0 0 220 101 290 A C ATOM 851 NZ LYS A 120 7.677−14.431 36.757 1.00 22.64 A N ANISOU 851 NZ LYS A 120 4052 2242 5342 35−275 13 A N SIGUIJ 851 NZ LYS A 120 1 0 0 221 61 289 A N ATOM 852 C LYSA 120 6.322 −7.836 34.835 1.00 14.75 A C ANISOU 852 C LYS A 120 17661360 1821 −282 −1 14 A C SIGUIJ 852 C LYS A 120 1 0 0 220 100 290 A CATOM 853 O LYS A 120 5.385 −8.141 34.071 1.00 14.75 A O ANISOU 853 O LYSA 120 1794 1689 1830 −381 1 −4 A O SIGUIJ 853 O LYS A 120 1 0 0 221 54289 A O ATOM 854 N VAL A 121 7.278 −6.993 34.497 1.00 13.48 A N ANISOU854 N VAL A 121 1616 1143 1653 −106 −1 −3 A N SIGUIJ 854 N VAL A 121 1 00 221 61 289 A N ATOM 855 CA VAL A 121 7.253 −6.364 33.174 1.00 13.91 AC ANISOU 855 CA VAL A 121 1816 1210 1670 −227 −55 38 A C SIGUIJ 855 CAVAL A 121 1 0 0 220 100 290 A C ATOM 856 CB VAL A 121 8.314 −5.20933.126 1.00 13.56 A C ANISOU 856 CB VAL A 121 1770 1166 1874 −183 −1 −1A C SIGUIJ 856 CB VAL A 121 1 0 0 220 100 290 A C ATOM 857 CG1 VAL A 1219.753 −5.773 32.994 1.00 13.96 A C ANISOU 857 CG1 VAL A 121 1784 11842409 −164 50 1 A C SIGUIJ 857 CG1 VAL A 121 1 0 0 220 100 290 A C ATOM858 CG2 VAL A 121 7.983 −4.239 32.010 1.00 13.81 A C ANISOU 858 CG2 VALA 121 1908 1183 1879 −146 −1 3 A C SIGUIJ 858 CG2 VAL A 121 1 0 0 220100 290 A C ATOM 859 C VAL A 121 7.593 −7.395 32.072 1.00 14.19 A CANISOU 859 C VAL A 121 1805 1241 1751 −314 16 −26 A C SIGUIJ 859 C VAL A121 1 0 0 220 100 290 A C ATOM 860 O VAL A 121 8.297 −8.355 32.317 1.0014.22 A O ANISOU 860 O VAL A 121 1970 1332 1922 −204 −9 12 A O SIGUIJ860 O VAL A 121 1 0 0 221 54 289 A O ATOM 861 N ARG A 122 7.115 −7.14530.859 1.00 15.04 A N ANISOU 861 N ARG A 122 1902 1439 1781 −380 −36 47A N SIGUIJ 861 N ARG A 122 1 0 0 221 61 289 A N ATOM 862 CA ARG A 1227.471 −7.987 29.718 1.00 16.06 A C ANISOU 862 CA ARG A 122 2015 15861913 −475 71 −103 A C SIGUIJ 862 CA ARG A 122 1 0 0 220 100 290 A C ATOM863 CB ARG A 122 6.305 −8.073 28.739 1.00 17.68 A C ANISOU 863 CB ARG A122 2071 2635 1977 −651 6 24 A C SIGUIJ 863 CB ARG A 122 1 0 0 220 100290 A C ATOM 864 CG ARG A 122 6.544 −9.094 27.666 1.00 20.19 A C ANISOU864 CG ARG A 122 3512 2743 2006 −306 3 −1 A C SIGUIJ 864 CG ARG A 122 10 0 220 100 290 A C ATOM 865 CD ARG A 122 5.253 −9.413 26.867 1.00 22.38A C ANISOU 865 CD ARG A 122 4419 9397 2928 −2250 −689 483 A C SIGUIJ 865CD ARG A 122 1 0 0 220 99 290 A C ATOM 866 NE ARG A 122 5.370 −10.38925.762 1.00 24.54 A N ANISOU 866 NE ARG A 122 16521 10017 3336 −1114−402 52 A N SIGUIJ 866 NE ARG A 122 1 0 0 221 61 289 A N ATOM 867 CZ ARGA 122 5.921 −11.604 25.812 1.00 25.24 A C ANISOU 867 CZ ARG A 122 1980210702 6450 339 −866 −27 A C SIGUIJ 867 CZ ARG A 122 1 0 0 220 99 290 A CATOM 868 NH1 ARG A 122 6.484 −12.073 26.931 1.00 26.18 A N ANISOU 868NH1 ARG A 122 14276 11218 5120 412 1934 164 A N SIGUIJ 868 NH1 ARG A 1221 0 0 221 61 289 A N ATOM 869 NH2 ARG A 122 5.850 −12.387 24.728 1.0025.97 A N ANISOU 869 NH2 ARG A 122 5520 10676 6376 380 43 −11 A N SIGUIJ869 NH2 ARG A 122 1 0 0 221 61 289 A N ATOM 870 C ARG A 122 8.683 −7.36129.040 1.00 15.84 A C ANISOU 870 C ARG A 122 1947 1450 1847 −377 11 −15A C SIGUIJ 870 C ARG A 122 1 0 0 220 99 290 A C ATOM 871 O ARG A 1228.602 −6.251 28.425 1.00 15.65 A O ANISOU 871 O ARG A 122 2349 1468 1918−374 −36 21 A O SIGUIJ 871 O ARG A 122 1 0 0 221 54 289 A O ATOM 872 NLEU A 123 9.801 −8.051 29.159 1.00 15.39 A N ANISOU 872 N LEU A 123 21191866 1765 −115 15 −5 A N SIGUIJ 872 N LEU A 123 1 0 0 221 61 289 A NATOM 873 CA LEU A 123 11.038 −7.618 28.518 1.00 15.70 A C ANISOU 873 CALEU A 123 2100 1663 1771 −34 16 −1 A C SIGUIJ 873 CA LEU A 123 1 0 0 22099 290 A C ATOM 874 CB LEU A 123 12.221 −8.340 29.185 1.00 15.74 A CANISOU 874 CB LEU A 123 2196 1845 1826 79 −20 −4 A C SIGUIJ 874 CB LEU A123 1 0 0 220 99 290 A C ATOM 875 CG LEU A 123 12.488 −7.891 30.640 1.0015.65 A C ANISOU 875 CG LEU A 123 2233 1901 1819 −18 −3 0 A C SIGUIJ 875CG LEU A 123 1 0 0 220 99 290 A C ATOM 876 CD1 LEU A 123 13.577 −8.78331.226 1.00 16.72 A C ANISOU 876 CD1 LEU A 123 3489 3126 2116 1193 −488−401 A C SIGUIJ 876 CD1 LEU A 123 1 0 0 220 99 290 A C ATOM 877 CD2 LEUA 123 12.911 −6.437 30.715 1.00 16.26 A C ANISOU 877 CD2 LEU A 123 21861902 2056 −19 −2 0 A C SIGUIJ 877 CD2 LEU A 123 1 0 0 220 99 290 A CATOM 878 C LEU A 123 10.950 −7.937 27.023 1.00 16.09 A C ANISOU 878 CLEU A 123 1925 1611 1775 59 8 2 A C SIGUIJ 878 C LEU A 123 1 0 0 220 99290 A C ATOM 879 O LEU A 123 10.185 −8.833 26.592 1.00 16.40 A O ANISOU879 O LEU A 123 2612 2183 1779 −574 96 −66 A O SIGUIJ 879 O LEU A 123 10 0 221 54 289 A O ATOM 880 N PRO A 124 11.700 −7.220 26.206 1.00 16.35A N ANISOU 880 N PRO A 124 1978 1672 1766 −4 −4 0 A N SIGUIJ 880 N PRO A124 1 0 0 221 61 289 A N ATOM 881 CD PRO A 124 12.624 −6.128 26.560 1.0015.91 A C ANISOU 881 CD PRO A 124 2031 1734 1615 −73 78 −16 A C SIGUIJ881 CD PRO A 124 1 0 0 220 99 290 A C ATOM 882 CA PRO A 124 11.586−7.385 24.754 1.00 17.20 A C ANISOU 882 CA PRO A 124 2443 1676 1767 −42−34 2 A C SIGUIJ 882 CA PRO A 124 1 0 0 220 98 290 A C ATOM 883 CB PRO A124 12.208 −6.094 24.205 1.00 16.17 A C ANISOU 883 CB PRO A 124 21521605 1773 101 −16 −4 A C SIGUIJ 883 CB PRO A 124 1 0 0 220 98 290 A CATOM 884 CG PRO A 124 13.248 −5.750 25.256 1.00 15.99 A C ANISOU 884 CGPRO A 124 2019 1617 1641 84 110 22 A C SIGUIJ 884 CG PRO A 124 1 0 0 22098 290 A C ATOM 885 C PRO A 124 12.337 −8.618 24.267 1.00 18.28 A CANISOU 885 C PRO A 124 3163 1858 1998 300 192 45 A C SIGUIJ 885 C PRO A124 1 0 0 220 98 290 A C ATOM 886 O PRO A 124 13.386 −8.981 24.829 1.0018.87 A O ANISOU 886 O PRO A 124 3346 1649 2602 279 −159 −43 A O SIGUIJ886 O PRO A 124 1 0 0 221 54 289 A O ATOM 887 N SER A 125 11.791 −9.24323.222 1.00 19.66 A N ANISOU 887 N SER A 125 3843 2018 2171 175 −77 −8 AN SIGUIJ 887 N SER A 125 1 0 0 221 61 289 A N ATOM 888 CA SER A 12512.571 −10.203 22.419 1.00 20.69 A C ANISOU 888 CA SER A 125 4056 18692511 35 286 9 A C SIGUIJ 888 CA SER A 125 1 0 0 220 98 290 A C ATOM 889CB SER A 125 11.778 −11.476 22.152 1.00 21.47 A C ANISOU 889 CB SER A125 5812 2535 3271 −1022 117 −40 A C SIGUIJ 889 CB SER A 125 1 0 0 22098 290 A C ATOM 890 OG SER A 125 10.598 −11.193 21.456 1.00 23.27 A OANISOU 890 OG SER A 125 6259 3583 4621 −942 −609 247 A O SIGUIJ 890 OGSER A 125 1 0 0 221 54 289 A O ATOM 891 C SER A 125 13.076 −9.643 21.0771.00 20.70 A C ANISOU 891 C SER A 125 4813 1956 2566 −188 474 −34 A CSIGUIJ 891 C SER A 125 1 0 0 220 98 290 A C ATOM 892 O SER A 125 13.944−10.244 20.430 1.00 21.30 A O ANISOU 892 O SER A 125 4931 1911 2914 −268699 −84 A O SIGUIJ 892 O SER A 125 1 0 0 221 54 289 A O ATOM 893 N ARG A128 12.552 −8.492 20.667 1.00 20.62 A N ANISOU 893 N ARG A 128 4284 18532191 −355 662 −99 A N SIGUIJ 893 N ARG A 128 1 0 0 221 61 289 A N ATOM894 CA ARG A 128 13.031 −7.806 19.477 1.00 20.32 A C ANISOU 894 CA ARG A128 3194 1797 2110 −112 365 −34 A C SIGUIJ 894 CA ARG A 128 1 0 0 220 98290 A C ATOM 895 CB ARG A 128 12.083 −8.091 18.318 1.00 21.53 A C ANISOU895 CB ARG A 128 4473 2586 2833 −575 −573 171 A C SIGUIJ 895 CB ARG A128 1 0 0 220 98 290 A C ATOM 896 CG ARG A 128 11.995 −9.586 17.993 1.0023.54 A C ANISOU 896 CG ARG A 128 15334 2629 3423 −1034 −1494 123 A CSIGUIJ 896 CG ARG A 128 1 0 0 220 98 290 A C ATOM 897 CD ARG A 12810.802 −9.845 17.097 1.00 24.98 A C ANISOU 897 CD ARG A 128 18087 123996545 −4248 −4147 1621 A C SIGUIJ 897 CD ARG A 128 1 0 0 220 97 290 A CATOM 898 NE ARG A 128 10.637 −8.686 16.229 1.00 26.43 A N ANISOU 898 NEARG A 128 19357 11868 3343 286 1652 51 A N SIGUIJ 898 NE ARG A 128 1 0 0221 61 289 A N ATOM 899 CZ ARG A 128 11.441 −8.423 15.203 1.00 26.81 A CANISOU 899 CZ ARG A 128 16526 8558 1782 1274 −336 −33 A C SIGUIJ 899 CZARG A 128 1 0 0 220 97 290 A C ATOM 900 NH1 ARG A 128 12.441 −9.26914.965 1.00 27.32 A N ANISOU 900 NH1 ARG A 128 16054 7639 4806 508 43723 A N SIGUIJ 900 NH1 ARG A 128 1 0 0 221 61 289 A N ATOM 901 NH2 ARG A128 11.249 −7.338 14.434 1.00 26.86 A N ANISOU 901 NH2 ARG A 128 40578229 1749 −729 −40 3 A N SIGUIJ 901 NH2 ARG A 128 1 0 0 221 61 289 A NATOM 902 C ARG A 128 13.053 −6.304 19.747 1.00 19.30 A C ANISOU 902 CARG A 128 2695 1789 1719 −36 33 −1 A C SIGUIJ 902 C ARG A 128 1 0 0 22097 290 A C ATOM 903 O ARG A 128 12.416 −5.831 20.708 1.00 19.07 A OANISOU 903 O ARG A 128 2890 2004 1722 150 62 9 A O SIGUIJ 903 O ARG A128 1 0 0 221 54 289 A O ATOM 904 N CYS A 129 13.757 −5.588 18.894 1.0018.42 A N ANISOU 904 N CYS A 129 2557 1768 1672 7 −39 0 A N SIGUIJ 904 NCYS A 129 1 0 0 221 61 289 A N ATOM 905 CA CYS A 129 13.825 −4.12418.956 1.00 17.61 A C ANISOU 905 CA CYS A 129 2220 1775 1665 23 −62 −3 AC SIGUIJ 905 CA CYS A 129 1 0 0 220 97 290 A C ATOM 906 C CYS A 12912.751 −3.513 18.078 1.00 17.14 A C ANISOU 906 C CYS A 129 2128 19641479 75 88 28 A C SIGUIJ 906 C CYS A 129 1 0 0 220 97 290 A C ATOM 907 OCYS A 129 12.690 −3.773 16.860 1.00 17.35 A O ANISOU 907 O CYS A 1292814 2211 1492 197 16 3 A O SIGUIJ 907 O CYS A 129 1 0 0 221 54 289 A OATOM 908 CB CYS A 129 15.170 −3.684 18.428 1.00 17.49 A C ANISOU 908 CBCYS A 129 2202 1672 1772 57 −59 −7 A C SIGUIJ 908 CB CYS A 129 1 0 0 22097 290 A C ATOM 909 SG CYS A 129 16.567 −4.357 19.370 1.00 17.33 A SANISOU 909 SG CYS A 129 2527 2258 1937 480 −253 −185 A S SIGUIJ 909 SGCYS A 129 1 0 0 221 48 289 A S ATOM 910 N GLU A 130 11.875 −2.719 18.6551.00 16.42 A N ANISOU 910 N GLU A 130 1991 1922 1399 −6 22 −1 A N SIGUIJ910 N GLU A 130 1 0 0 221 61 289 A N ATOM 911 CA GLU A 130 10.879 −2.00817.822 1.00 16.19 A C ANISOU 911 CA GLU A 130 2000 1988 1415 −1 −3 0 A CSIGUIJ 911 CA GLU A 130 1 0 0 220 97 290 A C ATOM 912 CB GLU A 130 9.741−1.429 18.687 1.00 16.86 A C ANISOU 912 CB GLU A 130 2205 2773 1438 39214 2 A C SIGUIJ 912 CB GLU A 130 1 0 0 220 97 290 A C ATOM 913 CG GLU A130 8.808 −2.483 19.317 1.00 19.01 A C ANISOU 913 CG GLU A 130 2557 31021342 33 −56 −6 A C SIGUIJ 913 CG GLU A 130 1 0 0 220 97 290 A C ATOM 914CD GLU A 130 7.994 −3.328 18.339 1.00 19.91 A C ANISOU 914 CD GLU A 1303068 3337 1719 −65 −404 −104 A C SIGUIJ 914 CD GLU A 130 1 0 0 220 97290 A C ATOM 915 OE1 GLU A 130 7.833 −2.865 17.179 1.00 20.94 A O ANISOU915 OE1 GLU A 130 2710 3803 1799 −221 −414 82 A O SIGUIJ 915 OE1 GLU A130 1 0 0 221 54 289 A O ATOM 916 OE2 GLU A 130 7.530 −4.438 18.743 1.0021.75 A O ANISOU 916 OE2 GLU A 130 4740 3706 2415 −733 −335 139 A OSIGUIJ 916 OE2 GLU A 130 1 0 0 221 54 289 A O ATOM 917 C GLU A 13011.549 −0.890 17.037 1.00 15.24 A C ANISOU 917 C GLU A 130 1918 19911348 10 −50 3 A C SIGUIJ 917 C GLU A 130 1 0 0 220 96 290 A C ATOM 918 OGLU A 130 12.429 −0.227 17.555 1.00 15.46 A O ANISOU 918 O GLU A 1301999 2010 1554 0 −184 11 A O SIGUIJ 918 O GLU A 130 1 0 0 221 54 289 A OATOM 919 N PRO A 131 11.143 −0.677 15.749 1.00 14.49 A N ANISOU 919 NPRO A 131 1826 2049 1323 37 −4 0 A N SIGUIJ 919 N PRO A 131 1 0 0 221 61289 A N ATOM 920 CD PRO A 131 10.218 −1.515 14.966 1.00 14.56 A C ANISOU920 CD PRO A 131 1943 2110 1393 −15 −84 −2 A C SIGUIJ 920 CD PRO A 131 10 0 220 96 290 A C ATOM 921 CA PRO A 131 11.842 0.294 14.898 1.00 13.90A C ANISOU 921 CA PRO A 131 1928 2069 1341 14 47 −3 A C SIGUIJ 921 CAPRO A 131 1 0 0 220 96 290 A C ATOM 922 CB PRO A 131 11.461 −0.11613.495 1.00 14.54 A C ANISOU 922 CB PRO A 131 2366 1951 1375 130 −87 −18A C SIGUIJ 922 CB PRO A 131 1 0 0 220 96 290 A C ATOM 923 CG PRO A 13110.119 −0.726 13.664 1.00 14.36 A C ANISOU 923 CG PRO A 131 2401 21051378 58 −81 −11 A C SIGUIJ 923 CG PRO A 131 1 0 0 220 96 290 A C ATOM924 C PRO A 131 11.405 1.728 15.135 1.00 13.68 A C ANISOU 924 C PRO A131 1793 2075 1235 7 −59 −1 A C SIGUIJ 924 C PRO A 131 1 0 0 220 96 290A C ATOM 925 O PRO A 131 10.293 1.971 15.604 1.00 13.49 A O ANISOU 925 OPRO A 131 1786 2141 1185 17 −73 −7 A O SIGUIJ 925 O PRO A 131 1 0 0 22154 289 A O ATOM 926 N PRO A 132 12.236 2.678 14.727 1.00 13.65 A NANISOU 926 N PRO A 132 1761 2065 1241 31 −62 1 A N SIGUIJ 926 N PRO A132 1 0 0 221 61 289 A N ATOM 927 CD PRO A 132 13.662 2.507 14.308 1.0013.98 A C ANISOU 927 CD PRO A 132 1800 2434 1629 75 49 2 A C SIGUIJ 927CD PRO A 132 1 0 0 220 96 290 A C ATOM 928 CA PRO A 132 11.820 4.05514.586 1.00 13.24 A C ANISOU 928 CA PRO A 132 1713 2054 1338 9 −165 −9 AC SIGUIJ 928 CA PRO A 132 1 0 0 220 96 290 A C ATOM 929 CB PRO A 13212.975 4.692 13.777 1.00 13.98 A C ANISOU 929 CB PRO A 132 1910 22971630 −115 22 −1 A C SIGUIJ 929 CB PRO A 132 1 0 0 220 96 290 A C ATOM930 CG PRO A 132 14.175 3.851 14.183 1.00 13.59 A C ANISOU 930 CG PRO A132 1983 2462 1533 0 47 −1 A C SIGUIJ 930 CG PRO A 132 1 0 0 220 96 290A C ATOM 931 C PRO A 132 10.480 4.149 13.876 1.00 13.22 A C ANISOU 931 CPRO A 132 1672 1663 1185 0 −83 −1 A C SIGUIJ 931 C PRO A 132 1 0 0 22095 290 A C ATOM 932 O PRO A 132 10.202 3.377 12.911 1.00 12.65 A OANISOU 932 O PRO A 132 1839 1675 1185 −16 −117 3 A O SIGUIJ 932 O PRO A132 1 0 0 221 54 289 A O ATOM 933 N GLY A 133 9.649 5.097 14.310 1.0012.65 A N ANISOU 933 N GLY A 133 1647 1646 1150 0 −123 −6 A N SIGUIJ 933N GLY A 133 1 0 0 221 61 289 A N ATOM 934 CA GLY A 133 8.320 5.25813.755 1.00 12.67 A C ANISOU 934 CA GLY A 133 1649 1779 1108 20 −106 8 AC SIGUIJ 934 CA GLY A 133 1 0 0 220 95 290 A C ATOM 935 C GLY A 1337.225 4.581 14.547 1.00 12.73 A C ANISOU 935 C GLY A 133 1724 1811 1198−9 −33 −1 A C SIGUIJ 935 C GLY A 133 1 0 0 220 95 290 A C ATOM 936 O GLYA 133 6.042 4.877 14.319 1.00 13.38 A O ANISOU 936 O GLY A 133 1756 21351334 80 −53 −1 A O SIGUIJ 936 O GLY A 133 1 0 0 221 54 289 A O ATOM 937N THR A 134 7.600 3.704 15.477 1.00 13.30 A N ANISOU 937 N THR A 1341756 1820 1198 −2 −27 −1 A N SIGUIJ 937 N THR A 134 1 0 0 221 61 289 A NATOM 938 CA THR A 134 6.617 3.030 16.301 1.00 13.30 A C ANISOU 938 CATHR A 134 1731 1806 1200 3 −37 1 A C SIGUIJ 938 CA THR A 134 1 0 0 22095 290 A C ATOM 939 CB THR A 134 7.235 1.798 16.938 1.00 13.36 A CANISOU 939 CB THR A 134 1759 1787 1244 −6 −84 −12 A C SIGUIJ 939 CB THRA 134 1 0 0 220 95 290 A C ATOM 940 OG1 THR A 134 7.779 0.970 15.9161.00 13.52 A O ANISOU 940 OG1 THR A 134 2156 1751 1418 −86 199 −33 A OSIGUIJ 940 OG1 THR A 134 1 0 0 221 54 289 A O ATOM 941 CG2 THR A 1346.197 0.987 17.718 1.00 14.12 A C ANISOU 941 CG2 THR A 134 2547 20221879 −383 580 −260 A C SIGUIJ 941 CG2 THR A 134 1 0 0 220 95 290 A CATOM 942 C THR A 134 6.095 3.992 17.394 1.00 13.61 A C ANISOU 942 C THRA 134 1677 1805 1200 −4 −46 −1 A C SIGUIJ 942 C THR A 134 1 0 0 220 95290 A C ATOM 943 O THR A 134 6.886 4.678 18.065 1.00 12.95 A O ANISOU943 O THR A 134 1695 1805 1240 −11 −73 −6 A O SIGUIJ 943 O THR A 134 1 00 221 54 289 A O ATOM 944 N THR A 135 4.776 4.050 17.591 1.00 13.92 A NANISOU 944 N THR A 135 1678 2130 1187 2 −57 −5 A N SIGUIJ 944 N THR A135 1 0 0 221 61 289 A N ATOM 945 CA THR A 135 4.168 4.738 18.736 1.0014.83 A C ANISOU 945 CA THR A 135 1958 2083 1256 −16 104 9 A C SIGUIJ945 CA THR A 135 1 0 0 220 95 290 A C ATOM 946 CB THR A 135 2.654 4.99818.466 1.00 15.90 A C ANISOU 946 CB THR A 135 2026 3624 1838 264 −17 −14A C SIGUIJ 946 CB THR A 135 1 0 0 220 95 290 A C ATOM 947 OG1 THR A 1352.510 5.931 17.384 1.00 18.22 A O ANISOU 947 OG1 THR A 135 3170 36401940 −12 −413 38 A O SIGUIJ 947 OG1 THR A 135 1 0 0 221 54 289 A O ATOM948 CG2 THR A 135 1.994 5.573 19.688 1.00 17.09 A C ANISOU 948 CG2 THR A135 2150 3585 1851 292 31 13 A C SIGUIJ 948 CG2 THR A 135 1 0 0 220 95290 A C ATOM 949 C THR A 135 4.320 3.966 20.031 1.00 14.33 A C ANISOU949 C THR A 135 1624 1974 1241 −200 52 −19 A C SIGUIJ 949 C THR A 135 10 0 220 95 290 A C ATOM 950 O THR A 135 4.113 2.746 20.078 1.00 14.51 AO ANISOU 950 O THR A 135 2619 2002 1444 −383 77 −31 A O SIGUIJ 950 O THRA 135 1 0 0 221 54 289 A O ATOM 951 N CYS A 136 4.776 4.666 21.062 1.0013.59 A N ANISOU 951 N CYS A 136 1558 1773 1249 −12 −20 −1 A N SIGUIJ951 N CYS A 136 1 0 0 221 61 289 A N ATOM 952 CA CYS A 136 5.015 4.06522.378 1.00 13.33 A C ANISOU 952 CA CYS A 136 1554 1725 1237 101 28 −5 AC SIGUIJ 952 CA CYS A 136 1 0 0 220 94 290 A C ATOM 953 C CYS A 1364.471 4.964 23.473 1.00 12.46 A C ANISOU 953 C CYS A 136 1464 1601 12290 37 2 A C SIGUIJ 953 C CYS A 136 1 0 0 220 94 290 A C ATOM 954 O CYS A136 4.032 6.090 23.209 1.00 12.45 A O ANISOU 954 O CYS A 136 1879 16561331 157 112 44 A O SIGUIJ 954 O CYS A 136 1 0 0 221 54 289 A O ATOM 955CB CYS A 136 6.509 3.869 22.590 1.00 14.29 A C ANISOU 955 CB CYS A 1361573 2489 1431 233 0 0 A C SIGUIJ 955 CB CYS A 136 1 0 0 220 94 290 A CATOM 956 SG CYS A 136 7.367 3.000 21.237 1.00 16.81 A S ANISOU 956 SGCYS A 136 2525 2969 1554 833 250 66 A S SIGUIJ 956 SG CYS A 136 1 0 0221 48 289 A S ATOM 957 N THR A 137 4.529 4.464 24.723 1.00 11.20 A NANISOU 957 N THR A 137 1477 1553 1216 −9 18 1 A N SIGUIJ 957 N THR A 1371 0 0 221 61 289 A N ATOM 958 CA THR A 137 4.042 5.275 25.863 1.00 11.13A C ANISOU 958 CA THR A 137 1388 1566 1178 −4 −44 −4 A C SIGUIJ 958 CATHR A 137 1 0 0 220 94 290 A C ATOM 959 CB THR A 137 2.808 4.631 26.4751.00 11.38 A C ANISOU 959 CB THR A 137 1492 1805 1290 −120 28 −6 A CSIGUIJ 959 CB THR A 137 1 0 0 220 94 290 A C ATOM 960 OG1 THR A 1371.772 4.518 25.474 1.00 12.96 A O ANISOU 960 OG1 THR A 137 1690 23191457 −189 −148 9 A O SIGUIJ 960 OG1 THR A 137 1 0 0 221 54 289 A O ATOM961 CG2 THR A 137 2.294 5.460 27.644 1.00 12.06 A C ANISOU 961 CG2 THR A137 1591 1848 1280 −27 3 0 A C SIGUIJ 961 CG2 THR A 137 1 0 0 220 94 290A C ATOM 962 C THR A 137 5.114 5.316 26.922 1.00 10.72 A C ANISOU 962 CTHR A 137 1358 1288 1131 −10 −4 0 A C SIGUIJ 962 C THR A 137 1 0 0 22094 290 A C ATOM 963 O THR A 137 5.701 4.302 27.259 1.00 10.60 A O ANISOU963 O THR A 137 1439 1299 1274 23 −53 −8 A O SIGUIJ 963 O THR A 137 1 00 221 54 289 A O ATOM 964 N AVAL A 138 5.393 6.508 27.426 0.50 10.12 A NANISOU 964 N AVAL A 138 1211 1281 1094 8 −3 0 A N SIGUIJ 964 N AVAL A138 1 0 0 221 60 289 A N ATOM 965 N BVAL A 138 5.385 6.512 27.428 0.5012.31 A N ANISOU 965 N BVAL A 138 1443 1286 1103 −4 −40 1 A N SIGUIJ 965N BVAL A 138 1 0 0 221 60 289 A N ATOM 966 CA AVAL A 138 6.324 6.70428.549 0.50 10.10 A C ANISOU 966 CA AVAL A 138 1182 1254 1073 6 9 0 A CSIGUIJ 966 CA AVAL A 138 1 0 0 220 94 290 A C ATOM 967 CA BVAL A 1386.312 6.716 28.551 0.50 12.29 A C ANISOU 967 CA BVAL A 138 1531 14441157 15 −118 −14 A C SIGUIJ 967 CA BVAL A 138 1 0 0 220 94 290 A C ATOM968 CB AVAL A 138 7.508 7.655 28.165 0.50 10.53 A C ANISOU 968 CB AVAL A138 1183 1243 957 10 −16 1 A C SIGUIJ 968 CB AVAL A 138 1 0 0 220 94 290A C ATOM 969 CB BVAL A 138 7.386 7.752 28.218 0.50 12.72 A C ANISOU 969CB BVAL A 138 1606 1489 1617 −11 0 0 A C SIGUIJ 969 CB BVAL A 138 1 0 0220 94 290 A C ATOM 970 CG1 AVAL A 138 7.015 9.028 27.740 0.50 12.13 A CANISOU 970 CG1 AVAL A 138 842 1196 916 −110 −4 −3 A C SIGUIJ 970 CG1AVAL A 138 1 0 0 220 93 290 A C ATOM 971 CG1 BVAL A 138 8.402 7.84929.353 0.50 14.32 A C ANISOU 971 CG1 BVAL A 138 1610 1933 1620 −51 0 0 AC SIGUIJ 971 CG1 BVAL A 138 1 0 0 220 93 290 A C ATOM 972 CG2 AVAL A 1388.490 7.746 29.329 0.50 11.37 A C ANISOU 972 CG2 AVAL A 138 1172 1688941 −47 5 0 A C SIGUIJ 972 CG2 AVAL A 138 1 0 0 220 93 290 A C ATOM 973CG2 BVAL A 138 8.073 7.365 26.963 0.50 13.56 A C ANISOU 973 CG2 BVAL A138 1626 1632 1622 1 0 0 A C SIGUIJ 973 CG2 BVAL A 138 1 0 0 220 93 290A C ATOM 974 C AVAL A 138 5.531 7.206 29.743 0.50 9.50 A C ANISOU 974 CAVAL A 138 1136 1216 1080 −7 6 0 A C SIGUIJ 974 C AVAL A 138 1 0 0 22093 290 A C ATOM 975 C BVAL A 138 5.507 7.183 29.746 0.50 11.69 A CANISOU 975 C BVAL A 138 1477 1210 1138 −57 −117 21 A C SIGUIJ 975 C BVALA 138 1 0 0 220 93 290 A C ATOM 976 O AVAL A 138 4.578 7.983 29.589 0.509.79 A O ANISOU 976 O AVAL A 138 1151 1246 1524 11 −36 3 A O SIGUIJ 976O AVAL A 138 1 0 0 221 54 289 A O ATOM 977 O BVAL A 138 4.527 7.92729.600 0.50 11.98 A O ANISOU 977 O BVAL A 138 1549 1334 1002 40 −111 −13A O SIGUIJ 977 O BVAL A 138 1 0 0 221 54 289 A O ATOM 978 N SER A 1395.937 6.742 30.928 1.00 9.56 A N ANISOU 978 N SER A 139 1291 1221 1099−1 −38 0 A N SIGUIJ 978 N SER A 139 1 0 0 221 60 289 A N ATOM 979 CA SERA 139 5.170 7.005 32.131 1.00 9.54 A C ANISOU 979 CA SER A 139 1324 12371118 8 −24 −2 A C SIGUIJ 979 CA SER A 139 1 0 0 220 93 290 A C ATOM 980CB SER A 139 4.269 5.812 32.461 1.00 10.03 A C ANISOU 980 CB SER A 1391401 1270 1287 −34 10 −3 A C SIGUIJ 980 CB SER A 139 1 0 0 220 93 290 AC ATOM 981 OG SER A 139 5.003 4.617 32.481 1.00 11.51 A O ANISOU 981 OGSER A 139 1459 1292 1644 −1 33 1 A O SIGUIJ 981 OG SER A 139 1 0 0 22154 289 A O ATOM 982 C SER A 139 6.078 7.354 33.297 1.00 9.22 A C ANISOU982 C SER A 139 1253 1054 1087 66 23 8 A C SIGUIJ 982 C SER A 139 1 0 0220 93 290 A C ATOM 983 O SER A 139 7.224 6.867 33.392 1.00 9.85 A OANISOU 983 O SER A 139 1281 1163 1307 117 0 4 A O SIGUIJ 983 O SER A 1391 0 0 221 54 289 A O ATOM 984 N GLY A 140 5.572 8.185 34.207 1.00 9.08 AN ANISOU 984 N GLY A 140 1119 1029 1087 −4 −2 0 A N SIGUIJ 984 N GLY A140 1 0 0 221 60 289 A N ATOM 985 CA GLY A 140 6.380 8.522 35.357 1.008.65 A C ANISOU 985 CA GLY A 140 1095 1033 1083 −2 1 0 A C SIGUIJ 985 CAGLY A 140 1 0 0 220 93 290 A C ATOM 986 C GLY A 140 5.665 9.494 36.2681.00 8.84 A C ANISOU 986 C GLY A 140 1080 1012 1076 13 0 0 A C SIGUIJ986 C GLY A 140 1 0 0 220 93 290 A C ATOM 987 O GLY A 140 4.631 10.08335.912 1.00 9.20 A O ANISOU 987 O GLY A 140 1154 1180 1100 132 0 2 A OSIGUIJ 987 O GLY A 140 1 0 0 221 54 289 A O ATOM 988 N TRP A 141 6.2989.713 37.416 1.00 8.37 A N ANISOU 988 N TRP A 141 1068 998 1071 1 0 0 AN SIGUIJ 988 N TRP A 141 1 0 0 221 60 289 A N ATOM 989 CA TRP A 1415.861 10.711 38.419 1.00 8.42 A C ANISOU 989 CA TRP A 141 1159 1028 108539 2 1 A C SIGUIJ 989 CA TRP A 141 1 0 0 220 92 290 A C ATOM 990 CB TRPA 141 5.863 10.071 39.821 1.00 8.68 A C ANISOU 990 CB TRP A 141 12351071 1094 −6 −19 1 A C SIGUIJ 990 CB TRP A 141 1 0 0 220 92 290 A C ATOM991 CG TRP A 141 4.815 9.037 40.046 1.00 9.31 A C ANISOU 991 CG TRP A141 1259 1093 1260 −23 0 0 A C SIGUIJ 991 CG TRP A 141 1 0 0 220 92 290A C ATOM 992 CD2 TRP A 141 4.973 7.599 40.033 1.00 9.94 A C ANISOU 992CD2 TRP A 141 1400 1092 1238 −27 −19 2 A C SIGUIJ 992 CD2 TRP A 141 1 00 220 92 290 A C ATOM 993 CE2 TRP A 141 3.721 7.036 40.431 1.00 10.38 AC ANISOU 993 CE2 TRP A 141 1454 1293 1265 −130 −3 2 A C SIGUIJ 993 CE2TRP A 141 1 0 0 220 92 290 A C ATOM 994 CE3 TRP A 141 6.041 6.729 39.7211.00 10.05 A C ANISOU 994 CE3 TRP A 141 1450 1194 1146 55 −80 −15 A CSIGUIJ 994 CE3 TRP A 141 1 0 0 220 92 290 A C ATOM 995 CD1 TRP A 1413.527 9.252 40.428 1.00 10.23 A C ANISOU 995 CD1 TRP A 141 1255 12661297 −1 −2 0 A C SIGUIJ 995 CD1 TRP A 141 1 0 0 220 92 290 A C ATOM 996NE1 TRP A 141 2.851 8.071 40.672 1.00 10.13 A N ANISOU 996 NE1 TRP A 1411458 1320 1352 −122 21 −17 A N SIGUIJ 996 NE1 TRP A 141 1 0 0 221 60 289A N ATOM 997 CZ2 TRP A 141 3.529 5.643 40.519 1.00 10.92 A C ANISOU 997CZ2 TRP A 141 1913 1299 1413 −192 −119 38 A C SIGUIJ 997 CZ2 TRP A 141 10 0 220 92 290 A C ATOM 998 CZ3 TRP A 141 5.811 5.348 39.810 1.00 10.75A C ANISOU 998 CZ3 TRP A 141 1928 1208 1483 −30 −130 8 A C SIGUIJ 998CZ3 TRP A 141 1 0 0 220 92 290 A C ATOM 999 CH2 TRP A 141 4.561 4.85040.207 1.00 11.25 A C ANISOU 999 CH2 TRP A 141 1969 1395 1465 −113 −12625 A C SIGUIJ 999 CH2 TRP A 141 1 0 0 220 92 290 A C ATOM 1000 C TRP A141 6.775 11.907 38.430 1.00 9.04 A C ANISOU 1000 C TRP A 141 1142 10161281 54 −4 0 A C SIGUIJ 1000 C TRP A 141 1 0 0 220 92 290 A C ATOM 1001O TRP A 141 6.708 12.694 39.416 1.00 9.10 A O ANISOU 1001 O TRP A 1411424 1075 1289 135 −48 −30 A O SIGUIJ 1001 O TRP A 141 1 0 0 221 54 289A O ATOM 1002 N GLY A 142 7.582 12.103 37.387 1.00 8.85 A N ANISOU 1002N GLY A 142 1106 950 1270 30 −28 −1 A N SIGUIJ 1002 N GLY A 142 1 0 0221 60 289 A N ATOM 1003 CA GLY A 142 8.438 13.273 37.308 1.00 9.39 A CANISOU 1003 CA GLY A 142 1130 971 1490 7 −14 0 A C SIGUIJ 1003 CA GLY A142 1 0 0 220 92 290 A C ATOM 1004 C GLY A 142 7.624 14.567 37.182 1.009.80 A C ANISOU 1004 C GLY A 142 1139 988 1262 15 4 0 A C SIGUIJ 1004 CGLY A 142 1 0 0 220 91 290 A C ATOM 1005 O GLY A 142 6.425 14.609 37.0011.00 9.72 A O ANISOU 1005 O GLY A 142 1138 1093 1291 4 −6 0 A O SIGUIJ1005 O GLY A 142 1 0 0 221 54 289 A O ATOM 1006 N THR A 143 8.368 15.66937.165 1.00 9.84 A N ANISOU 1006 N THR A 143 1165 993 1462 11 17 0 A NSIGUIJ 1006 N THR A 143 1 0 0 221 60 289 A N ATOM 1007 CA THR A 1437.699 16.969 37.095 1.00 10.27 A C ANISOU 1007 CA THR A 143 1258 10181345 54 3 −1 A C SIGUIJ 1007 CA THR A 143 1 0 0 220 91 290 A C ATOM 1008CB THR A 143 8.746 18.084 37.231 1.00 10.32 A C ANISOU 1008 CB THR A 1431204 970 1652 102 −17 0 A C SIGUIJ 1008 CB THR A 143 1 0 0 220 91 290 AC ATOM 1009 OG1 THR A 143 8.063 19.358 37.259 1.00 9.98 A O ANISOU 1009OG1 THR A 143 1329 1005 1727 174 −10 1 A O SIGUIJ 1009 OG1 THR A 143 1 00 221 54 289 A O ATOM 1010 CG2 THR A 143 9.814 18.077 36.102 1.00 11.20A C ANISOU 1010 CG2 THR A 143 1556 1474 1984 −12 329 −83 A C SIGUIJ 1010CG2 THR A 143 1 0 0 220 91 290 A C ATOM 1011 C THR A 143 6.907 17.09135.796 1.00 9.85 A C ANISOU 1011 C THR A 143 1261 1021 1340 16 −3 0 A CSIGUIJ 1011 C THR A 143 1 0 0 220 91 290 A C ATOM 1012 O THR A 143 7.31916.587 34.723 1.00 10.01 A O ANISOU 1012 O THR A 143 1366 1051 1335 64 22 A O SIGUIJ 1012 O THR A 143 1 0 0 221 54 289 A O ATOM 1013 N THR A 1445.791 17.825 35.914 1.00 10.36 A N ANISOU 1013 N THR A 144 1238 10021364 −10 6 0 A N SIGUIJ 1013 N THR A 144 1 0 0 221 60 289 A N ATOM 1014CA THR A 144 4.945 18.147 34.775 1.00 10.86 A C ANISOU 1014 CA THR A 1441287 1167 1390 23 −21 1 A C SIGUIJ 1014 CA THR A 144 1 0 0 220 91 290 AC ATOM 1015 CB THR A 144 3.454 17.993 35.145 1.00 10.86 A C ANISOU 1015CB THR A 144 1301 1280 1505 2 14 0 A C SIGUIJ 1015 CB THR A 144 1 0 0220 91 290 A C ATOM 1016 OG1 THR A 144 3.194 18.895 36.245 1.00 11.34 AO ANISOU 1016 OG1 THR A 144 1482 1318 1493 112 0 −2 A O SIGUIJ 1016 OG1THR A 144 1 0 0 221 54 289 A O ATOM 1017 CG2 THR A 144 3.171 16.58235.580 1.00 11.09 A C ANISOU 1017 CG2 THR A 144 1458 1289 1506 −29 2 0 AC SIGUIJ 1017 CG2 THR A 144 1 0 0 220 91 290 A C ATOM 1018 C THR A 1445.183 19.524 34.244 1.00 11.05 A C ANISOU 1018 C THR A 144 1315 11641433 14 −2 0 A C SIGUIJ 1018 C THR A 144 1 0 0 220 91 290 A C ATOM 1019O THR A 144 4.545 19.931 33.272 1.00 11.42 A O ANISOU 1019 O THR A 1441681 1258 1494 202 −153 −83 A O SIGUIJ 1019 O THR A 144 1 0 0 221 54 289A O ATOM 1020 N THR A 145 6.052 20.279 34.904 1.00 11.43 A N ANISOU 1020N THR A 145 1298 1103 1471 30 1 0 A N SIGUIJ 1020 N THR A 145 1 0 0 22160 289 A N ATOM 1021 CA THR A 145 6.405 21.640 34.524 1.00 12.02 A CANISOU 1021 CA THR A 145 1643 1128 1554 −73 3 −1 A C SIGUIJ 1021 CA THRA 145 1 0 0 220 91 290 A C ATOM 1022 CB THR A 145 5.840 22.676 35.5331.00 11.75 A C ANISOU 1022 CB THR A 145 1687 1177 1583 0 −1 0 A C SIGUIJ1022 CB THR A 145 1 0 0 220 91 290 A C ATOM 1023 OG1 THR A 145 6.30122.372 36.851 1.00 12.15 A O ANISOU 1023 OG1 THR A 145 1658 1383 1594119 2 2 A O SIGUIJ 1023 OG1 THR A 145 1 0 0 221 54 289 A O ATOM 1024 CG2THR A 145 4.316 22.694 35.480 1.00 12.43 A C ANISOU 1024 CG2 THR A 1451686 1575 2121 14 −22 −1 A C SIGUIJ 1024 CG2 THR A 145 1 0 0 220 91 290A C ATOM 1025 C THR A 145 7.915 21.777 34.499 1.00 13.22 A C ANISOU 1025C THR A 145 1651 1148 1958 −98 35 2 A C SIGUIJ 1025 C THR A 145 1 0 0220 90 290 A C ATOM 1026 O THR A 145 8.640 21.001 35.108 1.00 12.96 A OANISOU 1026 O THR A 145 1572 1279 1698 39 312 39 A O SIGUIJ 1026 O THR A145 1 0 0 221 54 289 A O ATOM 1027 N SER A 146 8.396 22.805 33.789 1.0014.32 A N ANISOU 1027 N SER A 146 2081 1240 1923 −316 13 −12 A N SIGUIJ1027 N SER A 146 1 0 0 221 60 289 A N ATOM 1028 CA SER A 146 9.82723.078 33.778 1.00 15.69 A C ANISOU 1028 CA SER A 146 2077 1369 2390−354 29 5 A C SIGUIJ 1028 CA SER A 146 1 0 0 220 90 290 A C ATOM 1029 CBSER A 146 10.531 22.074 32.828 1.00 15.13 A C ANISOU 1029 CB SER A 1461955 1414 2348 −341 −53 −21 A C SIGUIJ 1029 CB SER A 146 1 0 0 220 90290 A C ATOM 1030 OG SER A 146 11.947 22.136 32.948 1.00 15.26 A OANISOU 1030 OG SER A 146 1947 1494 1868 −352 −10 15 A O SIGUIJ 1030 OGSER A 146 1 0 0 221 54 289 A O ATOM 1031 C SER A 146 10.016 24.52933.296 1.00 16.96 A C ANISOU 1031 C SER A 146 2270 1385 2791 −317 274 89A C SIGUIJ 1031 C SER A 146 1 0 0 220 90 290 A C ATOM 1032 O SER A 1469.317 24.943 32.402 1.00 17.83 A O ANISOU 1032 O SER A 146 2835 17652966 26 −7 1 A O SIGUIJ 1032 O SER A 146 1 0 0 221 54 289 A O ATOM 1033N PRO A 147 10.984 25.281 33.888 1.00 18.13 A N ANISOU 1033 N PRO A 1472614 1723 3238 −579 48 25 A N SIGUIJ 1033 N PRO A 147 1 0 0 221 60 289 AN ATOM 1034 CD PRO A 147 11.203 26.695 33.477 1.00 18.57 A C ANISOU 1034CD PRO A 147 3321 1758 3547 −694 35 114 A C SIGUIJ 1034 CD PRO A 147 1 00 220 90 290 A C ATOM 1035 CA PRO A 147 11.935 24.865 34.919 1.00 18.91A C ANISOU 1035 CA PRO A 147 2366 1635 3105 −710 235 100 A C SIGUIJ 1035CA PRO A 147 1 0 0 220 90 290 A C ATOM 1036 CB PRO A 147 13.038 25.94134.860 1.00 18.92 A C ANISOU 1036 CB PRO A 147 2746 2035 3761 −1103 220172 A C SIGUIJ 1036 CB PRO A 147 1 0 0 220 90 290 A C ATOM 1037 CG PRO A147 12.247 27.120 34.449 1.00 19.82 A C ANISOU 1037 CG PRO A 147 33862206 3649 −752 −3 −16 A C SIGUIJ 1037 CG PRO A 147 1 0 0 220 90 290 A CATOM 1038 C PRO A 147 11.384 24.714 36.329 1.00 19.36 A C ANISOU 1038 CPRO A 147 2281 1841 3094 −744 184 101 A C SIGUIJ 1038 C PRO A 147 1 0 0220 90 290 A C ATOM 1039 O PRO A 147 12.027 24.088 37.151 1.00 20.21 A OANISOU 1039 O PRO A 147 3189 2435 3163 −54 1 −1 A O SIGUIJ 1039 O PRO A147 1 0 0 221 54 289 A O ATOM 1040 N ASP A 148 10.199 25.273 36.593 1.0019.73 A N ANISOU 1040 N ASP A 148 2484 2886 2571 −251 4 5 A N SIGUIJ1040 N ASP A 148 1 0 0 221 60 289 A N ATOM 1041 CA ASP A 148 9.53825.134 37.886 1.00 19.78 A C ANISOU 1041 CA ASP A 148 2418 2110 2565 −14−6 0 A C SIGUIJ 1041 CA ASP A 148 1 0 0 220 90 290 A C ATOM 1042 CB ASPA 148 8.234 25.937 37.938 1.00 21.32 A C ANISOU 1042 CB ASP A 148 24802280 3978 85 55 10 A C SIGUIJ 1042 CB ASP A 148 1 0 0 220 90 290 A CATOM 1043 CG ASP A 148 8.457 27.414 38.112 1.00 22.69 A C ANISOU 1043 CGASP A 148 3800 2314 4254 −113 3 0 A C SIGUIJ 1043 CG ASP A 148 1 0 0 22090 290 A C ATOM 1044 OD1 ASP A 148 9.587 27.828 38.379 1.00 24.07 A OANISOU 1044 OD1 ASP A 148 3948 2897 5492 −327 −284 −8 A O SIGUIJ 1044OD1 ASP A 148 1 0 0 221 54 289 A O ATOM 1045 OD2 ASP A 148 7.483 28.18837.967 1.00 24.12 A O ANISOU 1045 OD2 ASP A 148 4594 3226 11473 650−1275 −255 A O SIGUIJ 1045 OD2 ASP A 148 1 0 0 221 54 289 A O ATOM 1046C ASP A 148 9.206 23.661 38.078 1.00 18.72 A C ANISOU 1046 C ASP A 1481599 2068 2271 180 104 −31 A C SIGUIJ 1046 C ASP A 148 1 0 0 220 89 290A C ATOM 1047 O ASP A 148 8.798 22.986 37.114 1.00 18.78 A O ANISOU 1047O ASP A 148 2096 2187 2285 −13 21 2 A O SIGUIJ 1047 O ASP A 148 1 0 0221 54 289 A O ATOM 1048 N VAL A 149 9.477 23.118 39.260 1.00 17.60 A NANISOU 1048 N VAL A 149 1685 1907 2307 −149 −66 −24 A N SIGUIJ 1048 NVAL A 149 1 0 0 221 60 289 A N ATOM 1049 CA VAL A 149 9.117 21.72339.475 1.00 16.98 A C ANISOU 1049 CA VAL A 149 1519 1886 2609 −52 235−23 A C SIGUIJ 1049 CA VAL A 149 1 0 0 220 89 290 A C ATOM 1050 CB VAL A149 10.223 20.909 40.221 1.00 18.14 A C ANISOU 1050 CB VAL A 149 23613066 3460 690 −224 136 A C SIGUIJ 1050 CB VAL A 149 1 0 0 220 89 290 A CATOM 1051 CG1 VAL A 149 11.607 21.415 39.780 1.00 19.42 A C ANISOU 1051CG1 VAL A 149 2784 4089 5840 250 613 −77 A C SIGUIJ 1051 CG1 VAL A 149 10 0 220 89 290 A C ATOM 1052 CG2 VAL A 149 10.157 21.071 41.655 1.0018.89 A C ANISOU 1052 CG2 VAL A 149 2410 4172 3483 −116 −129 −11 A CSIGUIJ 1052 CG2 VAL A 149 1 0 0 220 89 290 A C ATOM 1053 C VAL A 1497.747 21.548 40.152 1.00 15.68 A C ANISOU 1053 C VAL A 149 1353 16011887 −25 −116 −11 A C SIGUIJ 1053 C VAL A 149 1 0 0 220 89 290 A C ATOM1054 O VAL A 149 7.386 22.235 41.125 1.00 15.49 A O ANISOU 1054 O VAL A149 1800 1636 1937 7 18 −1 A O SIGUIJ 1054 O VAL A 149 1 0 0 221 54 289A O ATOM 1055 N THR A 150 6.961 20.639 39.577 1.00 14.24 A N ANISOU 1055N THR A 150 1201 1560 1574 −12 94 3 A N SIGUIJ 1055 N THR A 150 1 0 0221 60 289 A N ATOM 1056 CA THR A 150 5.613 20.336 40.083 1.00 13.97 A CANISOU 1056 CA THR A 150 1203 1419 1588 9 92 −3 A C SIGUIJ 1056 CA THR A150 1 0 0 220 89 290 A C ATOM 1057 CB THR A 150 4.525 21.015 39.233 1.0013.75 A C ANISOU 1057 CB THR A 150 1382 1432 1892 16 −125 25 A C SIGUIJ1057 CB THR A 150 1 0 0 220 89 290 A C ATOM 1058 OG1 THR A 150 4.80922.402 39.136 1.00 13.44 A O ANISOU 1058 OG1 THR A 150 1530 1432 1779 322 0 A O SIGUIJ 1058 OG1 THR A 150 1 0 0 221 54 289 A O ATOM 1059 CG2THR A 150 3.156 20.866 39.871 1.00 14.02 A C ANISOU 1059 CG2 THR A 1501500 2153 2403 −76 116 11 A C SIGUIJ 1059 CG2 THR A 150 1 0 0 220 89 290A C ATOM 1060 C THR A 150 5.466 18.807 39.947 1.00 13.95 A C ANISOU 1060C THR A 150 1396 1421 1565 −4 26 2 A C SIGUIJ 1060 C THR A 150 1 0 0 22089 290 A C ATOM 1061 O THR A 150 5.425 18.253 38.819 1.00 13.25 A OANISOU 1061 O THR A 150 1375 1439 1553 2 22 0 A O SIGUIJ 1061 O THR A150 1 0 0 221 54 289 A O ATOM 1062 N PHE A 151 5.438 18.123 41.069 1.0014.35 A N ANISOU 1062 N PHE A 151 2376 1402 1568 −85 18 −2 A N SIGUIJ1062 N PHE A 151 1 0 0 221 60 289 A N ATOM 1063 CA PHE A 151 5.47916.635 41.088 1.00 14.74 A C ANISOU 1063 CA PHE A 151 2104 1402 1576 −90106 −15 A C SIGUIJ 1063 CA PHE A 151 1 0 0 220 89 290 A C ATOM 1064 CBPHE A 151 6.448 16.168 42.184 1.00 15.42 A C ANISOU 1064 CB PHE A 1512535 1967 1768 224 −141 −45 A C SIGUIJ 1064 CB PHE A 151 1 0 0 220 89290 A C ATOM 1065 CG PHE A 151 7.876 16.302 41.822 1.00 16.52 A C ANISOU1065 CG PHE A 151 2575 1771 2398 252 9 7 A C SIGUIJ 1065 CG PHE A 151 10 0 220 89 290 A C ATOM 1066 CD1 PHE A 151 8.715 17.164 42.537 1.0017.26 A C ANISOU 1066 CD1 PHE A 151 3798 2860 2442 −887 −54 34 A CSIGUIJ 1066 CD1 PHE A 151 1 0 0 220 88 290 A C ATOM 1067 CD2 PHE A 1518.421 15.591 40.804 1.00 16.32 A C ANISOU 1067 CD2 PHE A 151 2220 15742393 18 −23 1 A C SIGUIJ 1067 CD2 PHE A 151 1 0 0 220 88 290 A C ATOM1068 CE1 PHE A 151 10.046 17.272 42.212 1.00 17.77 A C ANISOU 1068 CE1PHE A 151 3814 3163 2595 −917 −4 3 A C SIGUIJ 1068 CE1 PHE A 151 1 0 0220 88 290 A C ATOM 1069 CE2 PHE A 151 9.756 15.708 40.467 1.00 16.62 AC ANISOU 1069 CE2 PHE A 151 2235 1615 2666 7 32 0 A C SIGUIJ 1069 CE2PHE A 151 1 0 0 220 88 290 A C ATOM 1070 CZ PHE A 151 10.587 16.55941.183 1.00 17.51 A C ANISOU 1070 CZ PHE A 151 3519 3053 2754 −1333 125−143 A C SIGUIJ 1070 CZ PHE A 151 1 0 0 220 88 290 A C ATOM 1071 C PHE A151 4.084 16.083 41.317 1.00 14.71 A C ANISOU 1071 C PHE A 151 2138 16511557 −198 138 −47 A C SIGUIJ 1071 C PHE A 151 1 0 0 220 88 290 A C ATOM1072 O PHE A 151 3.495 16.307 42.380 1.00 14.96 A O ANISOU 1072 O PHE A151 2406 1832 1649 −231 303 −94 A O SIGUIJ 1072 O PHE A 151 1 0 0 221 54289 A O ATOM 1073 N PRO A 152 3.497 15.385 40.340 1.00 14.27 A N ANISOU1073 N PRO A 152 1876 1307 1561 78 77 12 A N SIGUIJ 1073 N PRO A 152 1 00 221 60 289 A N ATOM 1074 CD PRO A 152 4.177 14.888 39.119 1.00 13.63 AC ANISOU 1074 CD PRO A 152 1704 1335 1524 105 −2 −1 A C SIGUIJ 1074 CDPRO A 152 1 0 0 220 88 290 A C ATOM 1075 CA PRO A 152 2.168 14.84340.478 1.00 14.57 A C ANISOU 1075 CA PRO A 152 1912 1581 1682 −23 48 −4A C SIGUIJ 1075 CA PRO A 152 1 0 0 220 88 290 A C ATOM 1076 CB PRO A 1521.834 14.420 39.050 1.00 13.80 A C ANISOU 1076 CB PRO A 152 1734 14701696 164 −4 −6 A C SIGUIJ 1076 CB PRO A 152 1 0 0 220 88 290 A C ATOM1077 CG PRO A 152 3.207 13.884 38.561 1.00 13.60 A C ANISOU 1077 CG PROA 152 1709 1342 1615 106 −9 −6 A C SIGUIJ 1077 CG PRO A 152 1 0 0 220 88290 A C ATOM 1078 C PRO A 152 2.094 13.623 41.416 1.00 14.68 A C ANISOU1078 C PRO A 152 1938 1582 1662 −28 5 0 A C SIGUIJ 1078 C PRO A 152 1 00 220 88 290 A C ATOM 1079 O PRO A 152 3.014 12.759 41.387 1.00 14.95 AO ANISOU 1079 O PRO A 152 2052 1731 1963 112 8 6 A O SIGUIJ 1079 O PRO A152 1 0 0 221 54 289 A O ATOM 1080 N ASER A 153 1.037 13.452 42.177 0.5014.75 A N ANISOU 1080 N ASER A 153 1941 1271 1662 36 17 2 A N SIGUIJ1080 N ASER A 153 1 0 0 221 60 289 A N ATOM 1081 N BSER A 153 1.02713.449 42.165 0.50 16.94 A N ANISOU 1081 N BSER A 153 1966 1686 1691 −3228 −3 A N SIGUIJ 1081 N BSER A 153 1 0 0 221 60 289 A N ATOM 1082 CAASER A 153 0.895 12.194 42.906 0.50 15.25 A C ANISOU 1082 CA ASER A 1531924 1273 1631 27 25 2 A C SIGUIJ 1082 CA ASER A 153 1 0 0 220 88 290 AC ATOM 1083 CA BSER A 153 0.874 12.194 42.901 0.50 17.44 A C ANISOU 1083CA BSER A 153 2666 1697 1679 −100 53 −5 A C SIGUIJ 1083 CA BSER A 153 10 0 220 88 290 A C ATOM 1084 CB ASER A 153 −0.131 12.364 44.038 0.5015.90 A C ANISOU 1084 CB ASER A 153 1966 1581 1640 104 50 14 A C SIGUIJ1084 CB ASER A 153 1 0 0 220 88 290 A C ATOM 1085 CB BSER A 153 −0.20312.347 43.970 0.50 18.09 A C ANISOU 1085 CB BSER A 153 3327 2368 2346−33 714 −24 A C SIGUIJ 1085 CB BSER A 153 1 0 0 220 87 290 A C ATOM 1086OG ASER A 153 0.274 13.375 44.962 0.50 17.70 A O ANISOU 1086 OG ASER A153 2449 1707 1640 −138 105 −18 A O SIGUIJ 1086 OG ASER A 153 1 0 0 22154 289 A O ATOM 1087 OG BSER A 153 −1.393 12.819 43.378 0.50 19.89 A OANISOU 1087 OG BSER A 153 3692 2488 3783 1 7 0 A O SIGUIJ 1087 OG BSER A153 1 0 0 221 54 289 A O ATOM 1088 C ASER A 153 0.491 11.031 42.001 0.5014.78 A C ANISOU 1088 C ASER A 153 2083 1334 1618 −109 123 −22 A CSIGUIJ 1088 C ASER A 153 1 0 0 220 87 290 A C ATOM 1089 C BSER A 1530.498 11.033 41.995 0.50 16.97 A C ANISOU 1089 C BSER A 153 2117 16501628 21 133 6 A C SIGUIJ 1089 C BSER A 153 1 0 0 220 87 290 A C ATOM1090 O ASER A 153 0.821 9.878 42.297 0.50 14.89 A O ANISOU 1090 O ASER A153 2390 1392 1506 64 444 27 A O SIGUIJ 1090 O ASER A 153 1 0 0 221 54289 A O ATOM 1091 O BSER A 153 0.837 9.883 42.290 0.50 17.08 A O ANISOU1091 O BSER A 153 2077 1631 1788 −18 54 −3 A O SIGUIJ 1091 O BSER A 1531 0 0 221 54 289 A O ATOM 1092 N ASP A 154 −0.215 11.329 40.913 1.0014.61 A N ANISOU 1092 N ASP A 154 1867 1602 1507 −21 292 −15 A N SIGUIJ1092 N ASP A 154 1 0 0 221 60 289 A N ATOM 1093 CA ASP A 154 −0.71610.259 40.073 1.00 14.15 A C ANISOU 1093 CA ASP A 154 1829 1493 1506 129111 39 A C SIGUIJ 1093 CA ASP A 154 1 0 0 220 87 290 A C ATOM 1094 CBASP A 154 −2.133 10.547 39.606 1.00 16.72 A C ANISOU 1094 CB ASP A 1542039 2560 3065 290 −403 134 A C SIGUIJ 1094 CB ASP A 154 1 0 0 220 87290 A C ATOM 1095 CG ASP A 154 −3.149 10.212 40.698 1.00 18.51 A CANISOU 1095 CG ASP A 154 3092 3865 3820 −195 421 100 A C SIGUIJ 1095 CGASP A 154 1 0 0 220 87 290 A C ATOM 1096 OD1 ASP A 154 −2.736 9.96441.855 1.00 20.68 A O ANISOU 1096 OD1 ASP A 154 5297 7688 3945 2014 103129 A O SIGUIJ 1096 OD1 ASP A 154 1 0 0 221 54 289 A O ATOM 1097 OD2 ASPA 154 −4.292 10.177 40.392 1.00 20.27 A O ANISOU 1097 OD2 ASP A 154 31263468 4265 −180 296 83 A O SIGUIJ 1097 OD2 ASP A 154 1 0 0 221 54 289 A OATOM 1098 C ASP A 154 0.217 10.035 38.916 1.00 13.00 A C ANISOU 1098 CASP A 154 1619 1251 1396 54 −30 −6 A C SIGUIJ 1098 C ASP A 154 1 0 0 22087 290 A C ATOM 1099 O ASP A 154 0.732 10.987 38.317 1.00 13.08 A OANISOU 1099 O ASP A 154 1725 1288 1483 35 25 3 A O SIGUIJ 1099 O ASP A154 1 0 0 221 53 289 A O ATOM 1100 N LEU A 155 0.431 8.750 38.591 1.0011.46 A N ANISOU 1100 N LEU A 155 1268 1229 1300 −2 1 0 A N SIGUIJ 1100N LEU A 155 1 0 0 221 60 289 A N ATOM 1101 CA LEU A 155 1.333 8.39637.482 1.00 10.69 A C ANISOU 1101 CA LEU A 155 1278 1173 1299 9 0 0 A CSIGUIJ 1101 CA LEU A 155 1 0 0 220 87 290 A C ATOM 1102 CB LEU A 1551.323 6.886 37.354 1.00 10.62 A C ANISOU 1102 CB LEU A 155 1357 11701476 13 3 0 A C SIGUIJ 1102 CB LEU A 155 1 0 0 220 87 290 A C ATOM 1103CG LEU A 155 2.321 6.294 36.341 1.00 10.20 A C ANISOU 1103 CG LEU A 1551369 1216 1468 42 −1 0 A C SIGUIJ 1103 CG LEU A 155 1 0 0 220 87 290 A CATOM 1104 CD1 LEU A 155 3.766 6.518 36.795 1.00 10.47 A C ANISOU 1104CD1 LEU A 155 1368 1430 1437 3 3 0 A C SIGUIJ 1104 CD1 LEU A 155 1 0 0220 87 290 A C ATOM 1105 CD2 LEU A 155 2.044 4.778 36.195 1.00 10.77 A CANISOU 1105 CD2 LEU A 155 1559 1219 1641 13 0 0 A C SIGUIJ 1105 CD2 LEUA 155 1 0 0 220 87 290 A C ATOM 1106 C LEU A 155 0.811 9.022 36.189 1.0010.49 A C ANISOU 1106 C LEU A 155 1245 1164 1304 −10 6 0 A C SIGUIJ 1106C LEU A 155 1 0 0 220 87 290 A C ATOM 1107 O LEU A 155 −0.371 8.88235.838 1.00 11.28 A O ANISOU 1107 O LEU A 155 1258 1519 1419 −58 −15 −4A O SIGUIJ 1107 O LEU A 155 1 0 0 221 53 289 A O ATOM 1108 N MET A 1561.690 9.655 35.433 1.00 9.99 A N ANISOU 1108 N MET A 156 1204 1082 127346 1 0 A N SIGUIJ 1108 N MET A 156 1 0 0 221 60 289 A N ATOM 1109 CA META 156 1.326 10.323 34.195 1.00 10.37 A C ANISOU 1109 CA MET A 156 12541102 1270 11 0 0 A C SIGUIJ 1109 CA MET A 156 1 0 0 220 86 290 A C ATOM1110 CB MET A 156 1.875 11.741 34.143 1.00 10.66 A C ANISOU 1110 CB META 156 1241 1089 1358 18 15 0 A C SIGUIJ 1110 CB MET A 156 1 0 0 220 86290 A C ATOM 1111 CG MET A 156 1.422 12.569 35.306 1.00 10.75 A C ANISOU1111 CG MET A 156 1467 1129 1354 172 19 16 A C SIGUIJ 1111 CG MET A 1561 0 0 220 86 290 A C ATOM 1112 SD MET A 156 −0.367 12.913 35.257 1.0011.95 A S ANISOU 1112 SD MET A 156 1475 1478 1716 248 47 −47 A S SIGUIJ1112 SD MET A 156 1 0 0 221 48 289 A S ATOM 1113 CE MET A 156 −0.40414.362 34.145 1.00 12.88 A C ANISOU 1113 CE MET A 156 2145 1524 1792 2316 3 A C SIGUIJ 1113 CE MET A 156 1 0 0 220 86 290 A C ATOM 1114 C MET A156 1.926 9.535 33.003 1.00 10.18 A C ANISOU 1114 C MET A 156 1229 11161253 −4 0 0 A C SIGUIJ 1114 C MET A 156 1 0 0 220 86 290 A C ATOM 1115 OMET A 156 2.974 8.862 33.116 1.00 9.91 A O ANISOU 1115 O MET A 156 12471152 1350 13 −13 0 A O SIGUIJ 1115 O MET A 156 1 0 0 221 53 289 A O ATOM1116 N CYS A 157 1.241 9.621 31.862 1.00 11.22 A N ANISOU 1116 N CYS A157 1250 1483 1243 112 2 −8 A N SIGUIJ 1116 N CYS A 157 1 0 0 221 60 289A N ATOM 1117 CA CYS A 157 1.515 8.880 30.626 1.00 12.15 A C ANISOU 1117CA CYS A 157 2256 1482 1236 275 149 44 A C SIGUIJ 1117 CA CYS A 157 1 00 220 86 290 A C ATOM 1118 C CYS A 157 1.524 9.860 29.448 1.00 11.80 A CANISOU 1118 C CYS A 157 1292 1434 1196 50 −9 −1 A C SIGUIJ 1118 C CYS A157 1 0 0 220 86 290 A C ATOM 1119 O CYS A 157 0.675 10.782 29.398 1.0011.77 A O ANISOU 1119 O CYS A 157 1416 1540 1417 181 −10 23 A O SIGUIJ1119 O CYS A 157 1 0 0 221 53 289 A O ATOM 1120 CB CYS A 157 0.356 7.83430.350 1.00 13.74 A C ANISOU 1120 CB CYS A 157 2508 1751 1748 47 47 3 AC SIGUIJ 1120 CB CYS A 157 1 0 0 220 86 290 A C ATOM 1121 SG CYS A 1570.673 6.233 31.156 1.00 16.07 A S ANISOU 1121 SG CYS A 157 2211 17531968 −138 −181 62 A S SIGUIJ 1121 SG CYS A 157 1 0 0 221 48 289 A S ATOM1122 N VAL A 158 2.415 9.642 28.483 1.00 11.72 A N ANISOU 1122 N VAL A158 1299 1378 1182 5 −8 0 A N SIGUIJ 1122 N VAL A 158 1 0 0 221 60 289 AN ATOM 1123 CA VAL A 158 2.293 10.363 27.243 1.00 12.28 A C ANISOU 1123CA VAL A 158 1705 1408 1171 110 18 5 A C SIGUIJ 1123 CA VAL A 158 1 0 0220 86 290 A C ATOM 1124 CB VAL A 158 3.136 11.684 27.278 1.00 13.24 A CANISOU 1124 CB VAL A 158 1959 1516 1902 −48 −1 0 A C SIGUIJ 1124 CB VALA 158 1 0 0 220 86 290 A C ATOM 1125 CG1 VAL A 158 4.608 11.418 27.2961.00 13.74 A C ANISOU 1125 CG1 VAL A 158 1957 1569 1947 −44 0 0 A CSIGUIJ 1125 CG1 VAL A 158 1 0 0 220 86 290 A C ATOM 1126 CG2 VAL A 1582.745 12.647 26.178 1.00 14.77 A C ANISOU 1126 CG2 VAL A 158 4568 16911967 560 −391 −77 A C SIGUIJ 1126 CG2 VAL A 158 1 0 0 220 86 290 A CATOM 1127 C VAL A 158 2.751 9.425 26.128 1.00 12.41 A C ANISOU 1127 CVAL A 158 1430 1350 1159 −17 5 −1 A C SIGUIJ 1127 C VAL A 158 1 0 0 22086 290 A C ATOM 1128 O VAL A 158 3.652 8.600 26.272 1.00 12.16 A OANISOU 1128 O VAL A 158 1502 1396 1358 35 −88 −21 A O SIGUIJ 1128 O VALA 158 1 0 0 221 53 289 A O ATOM 1129 N ASP A 159 2.086 9.578 24.965 1.0012.76 A N ANISOU 1129 N ASP A 159 1584 1656 1198 20 −77 13 A N SIGUIJ1129 N ASP A 159 1 0 0 221 60 289 A N ATOM 1130 CA ASP A 159 2.497 8.81123.777 1.00 13.37 A C ANISOU 1130 CA ASP A 159 1598 1673 1204 −8 −52 −2A C SIGUIJ 1130 CA ASP A 159 1 0 0 220 86 290 A C ATOM 1131 CB ASP A 1591.267 8.420 22.927 1.00 14.74 A C ANISOU 1131 CB ASP A 159 1857 24221533 −246 −301 42 A C SIGUIJ 1131 CB ASP A 159 1 0 0 220 86 290 A C ATOM1132 CG ASP A 159 0.493 7.286 23.548 1.00 16.02 A C ANISOU 1132 CG ASP A159 2007 2337 1862 −160 34 −15 A C SIGUIJ 1132 CG ASP A 159 1 0 0 220 85290 A C ATOM 1133 OD1 ASP A 159 0.719 6.893 24.717 1.00 16.45 A O ANISOU1133 OD1 ASP A 159 2215 2464 1870 −62 17 0 A O SIGUIJ 1133 OD1 ASP A 1591 0 0 221 53 289 A O ATOM 1134 OD2 ASP A 159 −0.351 6.719 22.834 1.0018.29 A O ANISOU 1134 OD2 ASP A 159 5074 4532 2734 −2701 −1569 1271 A OSIGUIJ 1134 OD2 ASP A 159 1 0 0 221 53 289 A O ATOM 1135 C ASP A 1593.493 9.567 22.905 1.00 13.43 A C ANISOU 1135 C ASP A 159 1654 1629 12843 36 2 A C SIGUIJ 1135 C ASP A 159 1 0 0 220 85 290 A C ATOM 1136 O ASPA 159 3.303 10.759 22.627 1.00 13.53 A O ANISOU 1136 O ASP A 159 19651636 1365 27 −70 −4 A O SIGUIJ 1136 O ASP A 159 1 0 0 221 53 289 A OATOM 1137 N VAL A 160 4.533 8.860 22.468 1.00 13.40 A N ANISOU 1137 NVAL A 160 1625 1614 1169 0 16 0 A N SIGUIJ 1137 N VAL A 160 1 0 0 221 60289 A N ATOM 1138 CA VAL A 160 5.576 9.460 21.670 1.00 13.93 A C ANISOU1138 CA VAL A 160 1688 1606 1314 7 131 10 A C SIGUIJ 1138 CA VAL A 160 10 0 220 85 290 A C ATOM 1139 CB VAL A 160 6.792 9.849 22.569 1.00 13.94A C ANISOU 1139 CB VAL A 160 1836 1945 1543 −94 −38 −4 A C SIGUIJ 1139CB VAL A 160 1 0 0 220 85 290 A C ATOM 1140 CG1 VAL A 160 6.462 11.11923.411 1.00 14.40 A C ANISOU 1140 CG1 VAL A 160 2351 2011 1859 −197 319−127 A C SIGUIJ 1140 CG1 VAL A 160 1 0 0 220 85 290 A C ATOM 1141 CG2VAL A 160 7.188 8.695 23.499 1.00 14.36 A C ANISOU 1141 CG2 VAL A 1602235 1984 1618 −33 −139 13 A C SIGUIJ 1141 CG2 VAL A 160 1 0 0 220 85290 A C ATOM 1142 C VAL A 160 6.039 8.422 20.663 1.00 14.44 A C ANISOU1142 C VAL A 160 1886 1637 1361 −2 225 −19 A C SIGUIJ 1142 C VAL A 160 10 0 220 85 290 A C ATOM 1143 O VAL A 160 5.843 7.199 20.854 1.00 14.89 AO ANISOU 1143 O VAL A 160 2763 1635 1732 −86 614 −37 A O SIGUIJ 1143 OVAL A 160 1 0 0 221 53 289 A O ATOM 1144 N ALYS A 161 6.709 8.880 19.6160.50 14.82 A N ANISOU 1144 N ALYS A 161 1721 1923 1271 −115 77 8 A NSIGUIJ 1144 N ALYS A 161 1 0 0 221 60 289 A N ATOM 1145 N BLYS A 1616.739 8.891 19.639 0.50 17.01 A N ANISOU 1145 N BLYS A 161 1678 19441216 −153 15 0 A N SIGUIJ 1145 N BLYS A 161 1 0 0 221 60 289 A N ATOM1146 CA ALYS A 161 7.140 7.989 18.553 0.50 15.17 A C ANISOU 1146 CA ALYSA 161 1807 2002 1245 13 7 −1 A C SIGUIJ 1146 CA ALYS A 161 1 0 0 220 85290 A C ATOM 1147 CA BLYS A 161 7.167 8.044 18.538 0.50 17.36 A C ANISOU1147 CA BLYS A 161 1866 2045 1191 22 −24 1 A C SIGUIJ 1147 CA BLYS A 1611 0 0 220 85 290 A C ATOM 1148 CB ALYS A 161 6.749 8.600 17.194 0.5016.95 A C ANISOU 1148 CB ALYS A 161 2060 2058 1278 −5 −79 21 A C SIGUIJ1148 CB ALYS A 161 1 0 0 220 85 290 A C ATOM 1149 CB BLYS A 161 6.8268.764 17.223 0.50 19.14 A C ANISOU 1149 CB BLYS A 161 3838 2063 1294 108−494 −25 A C SIGUIJ 1149 CB BLYS A 161 1 0 0 220 85 290 A C ATOM 1150 CGALYS A 161 5.437 8.043 16.545 0.50 19.34 A C ANISOU 1150 CG ALYS A 1612915 5131 1914 −1480 −539 360 A C SIGUIJ 1150 CG ALYS A 161 1 0 0 220 85290 A C ATOM 1151 CG BLYS A 161 7.117 7.965 15.951 0.50 21.53 A C ANISOU1151 CG BLYS A 161 3547 1785 1294 −348 −276 47 A C SIGUIJ 1151 CG BLYS A161 1 0 0 220 85 290 A C ATOM 1152 CD ALYS A 161 5.332 8.488 15.063 0.5020.76 A C ANISOU 1152 CD ALYS A 161 4366 4204 1772 34 −188 −25 A CSIGUIJ 1152 CD ALYS A 161 1 0 0 220 85 290 A C ATOM 1153 CD BLYS A 1616.593 8.709 14.720 0.50 22.95 A C ANISOU 1153 CD BLYS A 161 4275 22161181 430 −112 −19 A C SIGUIJ 1153 CD BLYS A 161 1 0 0 220 85 290 A CATOM 1154 CE ALYS A 161 5.716 9.966 14.901 0.50 22.03 A C ANISOU 1154 CEALYS A 161 8184 4418 3039 −842 864 −158 A C SIGUIJ 1154 CE ALYS A 161 10 0 220 84 290 A C ATOM 1155 CE BLYS A 161 7.245 10.085 14.606 0.5024.22 A C ANISOU 1155 CE BLYS A 161 4538 2268 2011 316 0 0 A C SIGUIJ1155 CE BLYS A 161 1 0 0 220 84 290 A C ATOM 1156 NZ ALYS A 161 5.63310.480 13.492 0.50 23.07 A N ANISOU 1156 NZ ALYS A 161 9802 5323 3110434 1233 98 A N SIGUIJ 1156 NZ ALYS A 161 1 0 0 221 60 289 A N ATOM 1157NZ BLYS A 161 7.093 10.747 13.285 0.50 25.26 A N ANISOU 1157 NZ BLYS A161 3509 2200 2008 85 6 0 A N SIGUIJ 1157 NZ BLYS A 161 1 0 0 221 60 289A N ATOM 1158 C ALYS A 161 8.652 7.771 18.618 0.50 14.88 A C ANISOU 1158C ALYS A 161 1803 1893 1418 −6 15 0 A C SIGUIJ 1158 C ALYS A 161 1 0 0220 84 290 A C ATOM 1159 C BLYS A 161 8.672 7.780 18.617 0.50 17.07 A CANISOU 1159 C BLYS A 161 1857 1895 1357 1 −25 0 A C SIGUIJ 1159 C BLYS A161 1 0 0 220 84 290 A C ATOM 1160 O ALYS A 161 9.407 8.730 18.907 0.5014.76 A O ANISOU 1160 O ALYS A 161 1819 1897 1528 −9 −26 −1 A O SIGUIJ1160 O ALYS A 161 1 0 0 221 53 289 A O ATOM 1161 O BLYS A 161 9.4448.716 18.909 0.50 16.95 A O ANISOU 1161 O BLYS A 161 1871 1904 1438 −5−48 −4 A O SIGUIJ 1161 O BLYS A 161 1 0 0 221 53 289 A O ATOM 1162 N LEUA 162 9.111 6.539 18.367 1.00 14.53 A N ANISOU 1162 N LEU A 162 16371883 1170 −41 −184 −22 A N SIGUIJ 1162 N LEU A 162 1 0 0 221 60 289 A NATOM 1163 CA LEU A 162 10.540 6.245 18.423 1.00 14.97 A C ANISOU 1163 CALEU A 162 1641 1937 1336 −28 −196 −30 A C SIGUIJ 1163 CA LEU A 162 1 0 0220 84 290 A C ATOM 1164 CB LEU A 162 10.797 4.765 18.271 1.00 15.03 A CANISOU 1164 CB LEU A 162 2006 1945 1331 30 −92 −19 A C SIGUIJ 1164 CBLEU A 162 1 0 0 220 84 290 A C ATOM 1165 CG LEU A 162 10.240 3.91519.380 1.00 15.42 A C ANISOU 1165 CG LEU A 162 2416 2021 1397 −68 36 −4A C SIGUIJ 1165 CG LEU A 162 1 0 0 220 84 290 A C ATOM 1166 CD1 LEU A162 10.716 2.477 19.181 1.00 15.74 A C ANISOU 1166 CD1 LEU A 162 25522029 1560 −38 114 −6 A C SIGUIJ 1166 CD1 LEU A 162 1 0 0 220 84 290 A CATOM 1167 CD2 LEU A 162 10.693 4.416 20.755 1.00 15.28 A C ANISOU 1167CD2 LEU A 162 2820 1970 1440 −3 −127 0 A C SIGUIJ 1167 CD2 LEU A 162 1 00 220 84 290 A C ATOM 1168 C LEU A 162 11.304 6.935 17.295 1.00 15.37 AC ANISOU 1168 C LEU A 162 1833 1949 1447 5 −48 0 A C SIGUIJ 1168 C LEU A162 1 0 0 220 84 290 A C ATOM 1169 O LEU A 162 10.794 7.015 16.148 1.0015.52 A O ANISOU 1169 O LEU A 162 1829 2144 1445 −15 −39 0 A O SIGUIJ1169 O LEU A 162 1 0 0 221 53 289 A O ATOM 1170 N ILE A 163 12.498 7.43517.619 1.00 15.74 A N ANISOU 1170 N ILE A 163 1883 2260 1359 −125 −34 −3A N SIGUIJ 1170 N ILE A 163 1 0 0 221 60 289 A N ATOM 1171 CA ILE A 16313.354 8.202 16.719 1.00 16.21 A C ANISOU 1171 CA ILE A 163 1862 22001390 −53 2 0 A C SIGUIJ 1171 CA ILE A 163 1 0 0 220 84 290 A C ATOM 1172CB ILE A 163 13.472 9.672 17.202 1.00 15.92 A C ANISOU 1172 CB ILE A 1632120 2205 1412 −20 −124 −15 A C SIGUIJ 1172 CB ILE A 163 1 0 0 220 84290 A C ATOM 1173 CG2 ILE A 163 14.500 10.400 16.330 1.00 15.79 A CANISOU 1173 CG2 ILE A 163 2191 2218 1522 −2 −32 −1 A C SIGUIJ 1173 CG2ILE A 163 1 0 0 220 84 290 A C ATOM 1174 CG1 ILE A 163 12.117 10.38217.185 1.00 15.79 A C ANISOU 1174 CG1 ILE A 163 2130 2228 1603 0 −121 −1A C SIGUIJ 1174 CG1 ILE A 163 1 0 0 220 84 290 A C ATOM 1175 CD1 ILE A163 12.075 11.716 17.970 1.00 15.74 A C ANISOU 1175 CD1 ILE A 163 25392223 1621 −69 39 −6 A C SIGUIJ 1175 CD1 ILE A 163 1 0 0 220 84 290 A CATOM 1176 C ILE A 163 14.720 7.506 16.806 1.00 16.73 A C ANISOU 1176 CILE A 163 1831 2097 1548 −115 −3 0 A C SIGUIJ 1176 C ILE A 163 1 0 0 22083 290 A C ATOM 1177 O ILE A 163 15.248 7.225 17.902 1.00 16.91 A OANISOU 1177 O ILE A 163 1812 2195 1546 −43 21 −1 A O SIGUIJ 1177 O ILE A163 1 0 0 221 53 289 A O ATOM 1178 N ASER A 164 15.283 7.166 15.649 0.5017.54 A N ANISOU 1178 N ASER A 164 1955 2334 1556 13 11 0 A N SIGUIJ1178 N ASER A 164 1 0 0 221 60 289 A N ATOM 1179 N BSER A 164 15.2997.181 15.648 0.50 19.73 A N ANISOU 1179 N BSER A 164 2017 2399 1584 −1262 −5 A N SIGUIJ 1179 N BSER A 164 1 0 0 221 60 289 A N ATOM 1180 CAASER A 164 16.610 6.552 15.616 0.50 18.20 A C ANISOU 1180 CA ASER A 1641927 2198 1631 −47 11 0 A C SIGUIJ 1180 CA ASER A 164 1 0 0 220 83 290 AC ATOM 1181 CA BSER A 164 16.626 6.547 15.627 0.50 20.39 A C ANISOU 1181CA BSER A 164 2009 2396 1594 −21 53 1 A C SIGUIJ 1181 CA BSER A 164 1 00 220 83 290 A C ATOM 1182 CB ASER A 164 16.963 6.230 14.159 0.50 18.66A C ANISOU 1182 CB ASER A 164 2509 2259 1665 −37 143 −14 A C SIGUIJ 1182CB ASER A 164 1 0 0 220 83 290 A C ATOM 1183 CB BSER A 164 17.049 6.22814.188 0.50 20.85 A C ANISOU 1183 CB BSER A 164 2339 3908 1573 918 −59−42 A C SIGUIJ 1183 CB BSER A 164 1 0 0 220 83 290 A C ATOM 1184 OG ASERA 164 18.305 5.844 14.025 0.50 20.65 A O ANISOU 1184 OG ASER A 164 25162354 1592 −9 137 −6 A O SIGUIJ 1184 OG ASER A 164 1 0 0 221 53 289 A OATOM 1185 OG BSER A 164 17.503 7.408 13.543 0.50 22.84 A O ANISOU 1185OG BSER A 164 4086 4269 1212 −25 −553 −49 A O SIGUIJ 1185 OG BSER A 1641 0 0 221 53 289 A O ATOM 1186 C ASER A 164 17.670 7.497 16.218 0.5018.34 A C ANISOU 1186 C ASER A 164 2095 2445 1585 −265 48 −6 A C SIGUIJ1186 C ASER A 164 1 0 0 220 83 290 A C ATOM 1187 C BSER A 164 17.6727.493 16.228 0.50 20.53 A C ANISOU 1187 C BSER A 164 2139 2579 1570 −18866 −2 A C SIGUIJ 1187 C BSER A 164 1 0 0 220 83 290 A C ATOM 1188 O ASERA 164 17.544 8.711 16.080 0.50 18.24 A O ANISOU 1188 O ASER A 164 16892442 1801 −325 9 11 A O SIGUIJ 1188 O ASER A 164 1 0 0 221 53 289 A OATOM 1189 O BSER A 164 17.547 8.706 16.089 0.50 20.43 A O ANISOU 1189 OBSER A 164 1868 2576 1648 −238 −7 4 A O SIGUIJ 1189 O BSER A 164 1 0 0221 53 289 A O ATOM 1190 N PRO A 165 18.726 6.936 16.871 1.00 18.81 A NANISOU 1190 N PRO A 165 2149 2718 1539 −112 89 −4 A N SIGUIJ 1190 N PROA 165 1 0 0 221 60 289 A N ATOM 1191 CD PRO A 165 18.987 5.525 17.2131.00 18.76 A C ANISOU 1191 CD PRO A 165 2457 2721 1699 −69 −46 −3 A CSIGUIJ 1191 CD PRO A 165 1 0 0 220 83 290 A C ATOM 1192 CA PRO A 16519.775 7.824 17.374 1.00 19.57 A C ANISOU 1192 CA PRO A 165 2032 26681427 −48 195 −33 A C SIGUIJ 1192 CA PRO A 165 1 0 0 220 83 290 A C ATOM1193 CB PRO A 165 20.786 6.876 18.018 1.00 19.09 A C ANISOU 1193 CB PROA 165 2277 2742 1967 3 −109 9 A C SIGUIJ 1193 CB PRO A 165 1 0 0 220 83290 A C ATOM 1194 CG PRO A 165 20.466 5.504 17.491 1.00 19.35 A C ANISOU1194 CG PRO A 165 2468 2765 2015 −50 −98 −10 A C SIGUIJ 1194 CG PRO A165 1 0 0 220 83 290 A C ATOM 1195 C PRO A 165 20.380 8.674 16.265 1.0020.46 A C ANISOU 1195 C PRO A 165 2709 3180 1499 −561 189 70 A C SIGUIJ1195 C PRO A 165 1 0 0 220 83 290 A C ATOM 1196 O PRO A 165 20.723 9.84116.475 1.00 20.36 A O ANISOU 1196 O PRO A 165 2254 3139 2103 −399 −6 15A O SIGUIJ 1196 O PRO A 165 1 0 0 221 53 289 A O ATOM 1197 N GLN A 16620.476 8.111 15.063 1.00 21.46 A N ANISOU 1197 N GLN A 166 2181 34571534 −440 99 −28 A N SIGUIJ 1197 N GLN A 166 1 0 0 221 60 289 A N ATOM1198 CA GLN A 166 21.083 8.867 13.962 1.00 22.39 A C ANISOU 1198 CA GLNA 166 2032 3534 1614 −301 112 82 A C SIGUIJ 1198 CA GLN A 166 1 0 0 22083 290 A C ATOM 1199 CB GLN A 166 21.313 7.971 12.734 1.00 23.16 A CANISOU 1199 CB GLN A 166 3581 3767 1697 41 163 −25 A C SIGUIJ 1199 CBGLN A 166 1 0 0 220 83 290 A C ATOM 1200 CG GLN A 166 22.377 6.90812.923 1.00 24.35 A C ANISOU 1200 CG GLN A 166 3512 3675 2572 −51 33 4 AC SIGUIJ 1200 CG GLN A 166 1 0 0 220 83 290 A C ATOM 1201 CD GLN A 16621.923 5.716 13.746 1.00 25.19 A C ANISOU 1201 CD GLN A 166 5033 37072696 −308 498 −85 A C SIGUIJ 1201 CD GLN A 166 1 0 0 220 83 290 A C ATOM1202 OE1 GLN A 166 20.727 5.479 13.912 1.00 25.85 A O ANISOU 1202 OE1GLN A 166 5129 6361 2617 −825 467 14 A O SIGUIJ 1202 OE1 GLN A 166 1 0 0221 53 289 A O ATOM 1203 NE2 GLN A 166 22.885 4.959 14.268 1.00 26.18 AN ANISOU 1203 NE2 GLN A 166 7239 6079 4294 1731 −609 −394 A N SIGUIJ1203 NE2 GLN A 166 1 0 0 221 60 289 A N ATOM 1204 C GLN A 166 20.22110.037 13.575 1.00 22.75 A C ANISOU 1204 C GLN A 166 2587 3802 1480 9161 −2 A C SIGUIJ 1204 C GLN A 166 1 0 0 220 82 290 A C ATOM 1205 O GLN A166 20.709 10.983 12.975 1.00 23.16 A O ANISOU 1205 O GLN A 166 40064222 3316 40 1137 617 A O SIGUIJ 1205 O GLN A 166 1 0 0 221 53 289 A OATOM 1206 N ASP A 167 18.938 9.991 13.913 1.00 22.90 A N ANISOU 1206 NASP A 167 2602 3170 1754 108 135 0 A N SIGUIJ 1206 N ASP A 167 1 0 0 22160 289 A N ATOM 1207 CA ASP A 167 18.056 11.093 13.579 1.00 23.15 A CANISOU 1207 CA ASP A 167 3064 3415 2305 420 −80 −10 A C SIGUIJ 1207 CAASP A 167 1 0 0 220 82 290 A C ATOM 1208 CB ASP A 167 16.706 10.53813.068 1.00 24.27 A C ANISOU 1208 CB ASP A 167 3393 5992 1565 −639 200−15 A C SIGUIJ 1208 CB ASP A 167 1 0 0 220 82 290 A C ATOM 1209 CG ASP A167 16.877 9.635 11.810 1.00 25.43 A C ANISOU 1209 CG ASP A 167 56596095 1537 −5 55 −1 A C SIGUIJ 1209 CG ASP A 167 1 0 0 220 82 290 A CATOM 1210 OD1 ASP A 167 17.549 10.088 10.848 1.00 26.67 A O ANISOU 1210OD1 ASP A 167 6408 6339 1957 −7 580 105 A O SIGUIJ 1210 OD1 ASP A 167 10 0 221 53 289 A O ATOM 1211 OD2 ASP A 167 16.381 8.468 11.749 1.0026.53 A O ANISOU 1211 OD2 ASP A 167 5637 6082 4197 23 −291 5 A O SIGUIJ1211 OD2 ASP A 167 1 0 0 221 53 289 A O ATOM 1212 C ASP A 167 17.84912.040 14.763 1.00 22.74 A C ANISOU 1212 C ASP A 167 2535 3302 2299 15559 25 A C SIGUIJ 1212 C ASP A 167 1 0 0 220 82 290 A C ATOM 1213 O ASP A167 17.058 12.949 14.672 1.00 23.11 A O ANISOU 1213 O ASP A 167 51575350 2673 2471 408 362 A O SIGUIJ 1213 O ASP A 167 1 0 0 221 53 289 A OATOM 1214 N CYS A 168 18.565 11.819 15.863 1.00 21.84 A N ANISOU 1214 NCYS A 168 2657 2909 2338 110 −25 0 A N SIGUIJ 1214 N CYS A 168 1 0 0 22160 289 A N ATOM 1215 CA CYS A 168 18.455 12.574 17.109 1.00 21.29 A CANISOU 1215 CA CYS A 168 2458 2912 2337 10 18 1 A C SIGUIJ 1215 CA CYS A168 1 0 0 220 82 290 A C ATOM 1216 C CYS A 168 19.744 13.356 17.349 1.0021.19 A C ANISOU 1216 C CYS A 168 2440 2839 2561 37 −1 0 A C SIGUIJ 1216C CYS A 168 1 0 0 220 82 290 A C ATOM 1217 O CYS A 168 20.753 12.77917.774 1.00 21.33 A O ANISOU 1217 O CYS A 168 2350 2590 2614 −110 −8 −3A O SIGUIJ 1217 O CYS A 168 1 0 0 221 53 289 A O ATOM 1218 CB CYS A 16818.227 11.592 18.289 1.00 20.25 A C ANISOU 1218 CB CYS A 168 2799 29422314 22 38 0 A C SIGUIJ 1218 CB CYS A 168 1 0 0 220 82 290 A C ATOM 1219SG CYS A 168 17.637 12.381 19.813 1.00 19.44 A S ANISOU 1219 SG CYS A168 2305 2485 2228 −371 51 139 A S SIGUIJ 1219 SG CYS A 168 1 0 0 221 48289 A S ATOM 1220 N THR A 169 19.704 14.662 17.133 1.00 21.34 A N ANISOU1220 N THR A 169 2615 2832 2450 37 2 0 A N SIGUIJ 1220 N THR A 169 1 0 0221 60 289 A N ATOM 1221 CA THR A 169 20.939 15.446 17.084 1.00 21.34 AC ANISOU 1221 CA THR A 169 2648 2897 3004 −8 26 1 A C SIGUIJ 1221 CA THRA 169 1 0 0 220 82 290 A C ATOM 1222 CB THR A 169 20.619 16.869 16.6851.00 21.92 A C ANISOU 1222 CB THR A 169 3516 2947 3132 191 37 15 A CSIGUIJ 1222 CB THR A 169 1 0 0 220 82 290 A C ATOM 1223 OG1 THR A 16919.746 16.838 15.550 1.00 22.86 A O ANISOU 1223 OG1 THR A 169 3587 39243179 159 −15 0 A O SIGUIJ 1223 OG1 THR A 169 1 0 0 221 53 289 A O ATOM1224 CG2 THR A 169 21.905 17.637 16.423 1.00 22.13 A C ANISOU 1224 CG2THR A 169 3660 3327 3109 −45 39 −4 A C SIGUIJ 1224 CG2 THR A 169 1 0 0220 82 290 A C ATOM 1225 C THR A 169 21.691 15.465 18.390 1.00 21.07 A CANISOU 1225 C THR A 169 2190 2662 2837 −67 302 33 A C SIGUIJ 1225 C THRA 169 1 0 0 220 82 290 A C ATOM 1226 O THR A 169 22.905 15.517 18.3921.00 21.00 A O ANISOU 1226 O THR A 169 2187 2828 3303 −78 303 29 A OSIGUIJ 1226 O THR A 169 1 0 0 221 53 289 A O ATOM 1227 N LYS A 17020.975 15.412 19.523 1.00 20.57 A N ANISOU 1227 N LYS A 170 1891 26292700 −119 96 14 A N SIGUIJ 1227 N LYS A 170 1 0 0 221 60 289 A N ATOM1228 CA LYS A 170 21.672 15.507 20.806 1.00 20.13 A C ANISOU 1228 CA LYSA 170 1876 2497 2697 −38 92 5 A C SIGUIJ 1228 CA LYS A 170 1 0 0 220 82290 A C ATOM 1229 CB LYS A 170 20.709 15.882 21.943 1.00 19.74 A CANISOU 1229 CB LYS A 170 1824 2107 2682 −157 85 27 A C SIGUIJ 1229 CBLYS A 170 1 0 0 220 82 290 A C ATOM 1230 CG LYS A 170 19.604 14.81622.229 1.00 18.85 A C ANISOU 1230 CG LYS A 170 1779 2060 2249 −125 1 0 AC SIGUIJ 1230 CG LYS A 170 1 0 0 220 82 290 A C ATOM 1231 CD LYS A 17018.720 15.116 23.458 1.00 18.16 A C ANISOU 1231 CD LYS A 170 1837 22562256 −43 12 1 A C SIGUIJ 1231 CD LYS A 170 1 0 0 220 82 290 A C ATOM1232 CE LYS A 170 17.997 16.462 23.389 1.00 17.62 A C ANISOU 1232 CE LYSA 170 1895 2266 1848 −17 3 −1 A C SIGUIJ 1232 CE LYS A 170 1 0 0 220 82290 A C ATOM 1233 NZ LYS A 170 16.968 16.452 22.315 1.00 16.88 A NANISOU 1233 NZ LYS A 170 1898 1875 1853 −3 1 0 A N SIGUIJ 1233 NZ LYS A170 1 0 0 221 60 289 A N ATOM 1234 C LYS A 170 22.412 14.201 21.174 1.0020.06 A C ANISOU 1234 C LYS A 170 1567 2434 2438 −165 245 44 A C SIGUIJ1234 C LYS A 170 1 0 0 220 81 290 A C ATOM 1235 O LYS A 170 23.21714.193 22.112 1.00 20.45 A O ANISOU 1235 O LYS A 170 1997 3070 2753 −90−129 −13 A O SIGUIJ 1235 O LYS A 170 1 0 0 221 53 289 A O ATOM 1236 NVAL A 171 22.152 13.098 20.470 1.00 20.14 A N ANISOU 1236 N VAL A 1711835 2415 2364 −225 255 89 A N SIGUIJ 1236 N VAL A 171 1 0 0 221 60 289A N ATOM 1237 CA VAL A 171 22.895 11.853 20.727 1.00 20.53 A C ANISOU1237 CA VAL A 171 2282 2522 2780 −12 −61 −3 A C SIGUIJ 1237 CA VAL A 1711 0 0 220 81 290 A C ATOM 1238 CB VAL A 171 22.084 10.556 20.310 1.0020.49 A C ANISOU 1238 CB VAL A 171 2207 2520 2482 −16 71 4 A C SIGUIJ1238 CB VAL A 171 1 0 0 220 81 290 A C ATOM 1239 CG1 VAL A 171 22.9849.287 20.470 1.00 20.47 A C ANISOU 1239 CG1 VAL A 171 2247 2537 2636 829 −1 A C SIGUIJ 1239 CG1 VAL A 171 1 0 0 220 81 290 A C ATOM 1240 CG2VAL A 171 20.770 10.419 21.143 1.00 20.58 A C ANISOU 1240 CG2 VAL A 1712165 3658 2337 −151 −17 −8 A C SIGUIJ 1240 CG2 VAL A 171 1 0 0 220 81290 A C ATOM 1241 C VAL A 171 24.187 11.930 19.884 1.00 20.83 A C ANISOU1241 C VAL A 171 2346 3732 2925 −83 29 3 A C SIGUIJ 1241 C VAL A 171 1 00 220 81 290 A C ATOM 1242 O VAL A 171 24.131 12.259 18.675 1.00 21.72 AO ANISOU 1242 O VAL A 171 2571 3750 2925 47 63 −4 A O SIGUIJ 1242 O VALA 171 1 0 0 221 53 289 A O ATOM 1243 N GLU A 177 24.714 6.144 22.0611.00 30.45 A N ANISOU 1243 N GLU A 177 15233 5567 7403 2183 1205 295 A NSIGUIJ 1243 N GLU A 177 1 0 0 221 59 289 A N ATOM 1244 CA GLU A 17725.208 5.336 20.938 1.00 30.20 A C ANISOU 1244 CA GLU A 177 6599 36927053 −1437 11 52 A C SIGUIJ 1244 CA GLU A 177 1 0 0 220 81 290 A C ATOM1245 CB GLU A 177 26.280 4.351 21.409 1.00 30.89 A C ANISOU 1245 CB GLUA 177 8482 5844 7054 574 −73 −22 A C SIGUIJ 1245 CB GLU A 177 1 0 0 22081 290 A C ATOM 1246 CG GLU A 177 27.548 4.940 22.022 1.00 31.90 A CANISOU 1246 CG GLU A 177 8808 7402 6935 −165 −36 4 A C SIGUIJ 1246 CGGLU A 177 1 0 0 220 81 290 A C ATOM 1247 CD GLU A 177 28.257 3.88722.864 1.00 32.41 A C ANISOU 1247 CD GLU A 177 9329 7656 6884 219 11 1 AC SIGUIJ 1247 CD GLU A 177 1 0 0 220 81 290 A C ATOM 1248 OE1 GLU A 17727.734 2.734 22.885 1.00 33.04 A O ANISOU 1248 OE1 GLU A 177 10051 780017802 −100 605 −45 A O SIGUIJ 1248 OE1 GLU A 177 1 0 0 221 53 289 A OATOM 1249 OE2 GLU A 177 29.309 4.194 23.498 1.00 33.04 A O ANISOU 1249OE2 GLU A 177 9204 7747 6480 175 243 22 A O SIGUIJ 1249 OE2 GLU A 177 10 0 221 53 289 A O ATOM 1250 C GLU A 177 24.084 4.530 20.269 1.00 29.54A C ANISOU 1250 C GLU A 177 6277 2685 7931 −641 −409 −78 A C SIGUIJ 1250C GLU A 177 1 0 0 220 81 290 A C ATOM 1251 O GLU A 177 22.911 4.91420.319 1.00 29.57 A O ANISOU 1251 O GLU A 177 6388 3811 3113 −269 −56351 A O SIGUIJ 1251 O GLU A 177 1 0 0 221 53 289 A O ATOM 1252 N ASN A178 24.479 3.419 19.638 1.00 28.62 A N ANISOU 1252 N ASN A 178 9088 29478004 196 −131 −24 A N SIGUIJ 1252 N ASN A 178 1 0 0 221 59 289 A N ATOM1253 CA ASN A 178 23.571 2.477 18.981 1.00 27.24 A C ANISOU 1253 CA ASNA 178 7592 3769 4115 −488 2926 −271 A C SIGUIJ 1253 CA ASN A 178 1 0 0220 81 290 A C ATOM 1254 CB ASN A 178 24.352 1.495 18.067 1.00 28.13 A CANISOU 1254 CB ASN A 178 6290 3877 2567 −101 1381 −56 A C SIGUIJ 1254 CBASN A 178 1 0 0 220 81 290 A C ATOM 1255 CG ASN A 178 25.745 1.11918.625 1.00 28.73 A C ANISOU 1255 CG ASN A 178 6714 4665 4896 81 458 19A C SIGUIJ 1255 CG ASN A 178 1 0 0 220 81 290 A C ATOM 1256 OD1 ASN A178 26.192 1.636 19.666 1.00 29.72 A O ANISOU 1256 OD1 ASN A 178 84554754 5214 23 −259 −2 A O SIGUIJ 1256 OD1 ASN A 178 1 0 0 221 53 289 A OATOM 1257 ND2 ASN A 178 26.448 0.220 17.914 1.00 29.42 A N ANISOU 1257ND2 ASN A 178 7350 5001 4766 590 434 99 A N SIGUIJ 1257 ND2 ASN A 178 10 0 221 59 289 A N ATOM 1258 C ASN A 178 22.775 1.681 20.016 1.00 25.77A C ANISOU 1258 C ASN A 178 3575 3705 2238 −41 180 37 A C SIGUIJ 1258 CASN A 178 1 0 0 220 81 290 A C ATOM 1259 O ASN A 178 22.065 0.768 19.6601.00 26.06 A O ANISOU 1259 O ASN A 178 7055 7616 3835 −3753 2759 −2585 AO SIGUIJ 1259 O ASN A 178 1 0 0 221 53 289 A O ATOM 1260 N SER A 17922.896 2.009 21.299 1.00 23.67 A N ANISOU 1260 N SER A 179 2304 28172162 −205 341 260 A N SIGUIJ 1260 N SER A 179 1 0 0 221 59 289 A N ATOM1261 CA SER A 179 21.988 1.398 22.278 1.00 21.65 A C ANISOU 1261 CA SERA 179 1937 1871 1752 31 149 −112 A C SIGUIJ 1261 CA SER A 179 1 0 0 22081 290 A C ATOM 1262 CB SER A 179 22.760 0.577 23.301 1.00 21.87 A CANISOU 1262 CB SER A 179 2977 2792 1952 849 20 15 A C SIGUIJ 1262 CB SERA 179 1 0 0 220 81 290 A C ATOM 1263 OG SER A 179 23.751 1.382 23.8771.00 22.51 A O ANISOU 1263 OG SER A 179 3828 3864 2467 −1 −265 −14 A OSIGUIJ 1263 OG SER A 179 1 0 0 221 53 289 A O ATOM 1264 C SER A 17921.163 2.461 22.981 1.00 20.58 A C ANISOU 1264 C SER A 179 1866 17861496 27 89 17 A C SIGUIJ 1264 C SER A 179 1 0 0 220 80 290 A C ATOM 1265O SER A 179 20.666 2.225 24.082 1.00 19.04 A O ANISOU 1265 O SER A 1791600 1802 1451 −24 −42 −1 A O SIGUIJ 1265 O SER A 179 1 0 0 221 53 289 AO ATOM 1266 N MET A 180 21.010 3.603 22.317 1.00 19.80 A N ANISOU 1266 NMET A 180 2051 1818 1507 107 260 63 A N SIGUIJ 1266 N MET A 180 1 0 0221 59 289 A N ATOM 1267 CA MET A 180 20.080 4.634 22.752 1.00 19.86 A CANISOU 1267 CA MET A 180 2142 1852 1489 157 324 100 A C SIGUIJ 1267 CAMET A 180 1 0 0 220 80 290 A C ATOM 1268 CB MET A 180 20.877 5.88723.100 1.00 21.09 A C ANISOU 1268 CB MET A 180 2439 2022 2291 −55 297−47 A C SIGUIJ 1268 CB MET A 180 1 0 0 220 80 290 A C ATOM 1269 CG MET A180 21.722 5.649 24.370 1.00 22.71 A C ANISOU 1269 CG MET A 180 29533089 2523 123 −22 2 A C SIGUIJ 1269 CG MET A 180 1 0 0 220 80 290 A CATOM 1270 SD MET A 180 22.740 6.968 25.045 1.00 25.89 A S ANISOU 1270 SDMET A 180 3687 3461 4056 −155 −668 −263 A S SIGUIJ 1270 SD MET A 180 1 00 221 48 289 A S ATOM 1271 CE MET A 180 22.682 8.045 23.918 1.00 25.18 AC ANISOU 1271 CE MET A 180 2232 3732 4211 587 146 −47 A C SIGUIJ 1271 CEMET A 180 1 0 0 220 80 290 A C ATOM 1272 C MET A 180 19.024 4.912 21.6791.00 19.33 A C ANISOU 1272 C MET A 180 2299 2089 1567 219 212 98 A CSIGUIJ 1272 C MET A 180 1 0 0 220 80 290 A C ATOM 1273 O MET A 18019.264 4.704 20.467 1.00 18.97 A O ANISOU 1273 O MET A 180 2263 26501587 50 250 −36 A O SIGUIJ 1273 O MET A 180 1 0 0 221 53 289 A O ATOM1274 N LEU A 181 17.860 5.385 22.110 1.00 18.49 A N ANISOU 1274 N LEU A181 2227 1985 1333 141 80 24 A N SIGUIJ 1274 N LEU A 181 1 0 0 221 59289 A N ATOM 1275 CA LEU A 181 16.721 5.725 21.257 1.00 18.17 A C ANISOU1275 CA LEU A 181 2590 2084 1818 292 −347 −155 A C SIGUIJ 1275 CA LEU A181 1 0 0 220 80 290 A C ATOM 1276 CB LEU A 181 15.499 4.782 21.584 1.0019.17 A C ANISOU 1276 CB LEU A 181 2887 2534 3154 −22 −109 −2 A C SIGUIJ1276 CB LEU A 181 1 0 0 220 80 290 A C ATOM 1277 CG LEU A 181 15.4883.297 21.162 1.00 20.31 A C ANISOU 1277 CG LEU A 181 8681 2536 3196 113−741 −13 A C SIGUIJ 1277 CG LEU A 181 1 0 0 220 80 290 A C ATOM 1278 CD1LEU A 181 14.409 2.548 21.904 1.00 20.65 A C ANISOU 1278 CD1 LEU A 1818500 1489 3825 817 −292 −42 A C SIGUIJ 1278 CD1 LEU A 181 1 0 0 220 80290 A C ATOM 1279 CD2 LEU A 181 15.256 3.218 19.670 1.00 20.95 A CANISOU 1279 CD2 LEU A 181 3788 3211 3073 −175 35 −9 A C SIGUIJ 1279 CD2LEU A 181 1 0 0 220 80 290 A C ATOM 1280 C LEU A 181 16.361 7.163 21.6541.00 17.15 A C ANISOU 1280 C LEU A 181 1756 1968 1299 14 −130 7 A CSIGUIJ 1280 C LEU A 181 1 0 0 220 80 290 A C ATOM 1281 O LEU A 18116.578 7.556 22.811 1.00 16.13 A O ANISOU 1281 O LEU A 181 2236 19391308 50 −220 −20 A O SIGUIJ 1281 O LEU A 181 1 0 0 221 53 289 A O ATOM1282 N CYS A 182 15.733 7.938 20.767 1.00 15.93 A N ANISOU 1282 N CYS A182 1636 1977 1252 15 −62 0 A N SIGUIJ 1282 N CYS A 182 1 0 0 221 59 289A N ATOM 1283 CA CYS A 182 14.999 9.120 21.204 1.00 15.01 A C ANISOU1283 CA CYS A 182 1496 1914 1462 −93 3 −6 A C SIGUIJ 1283 CA CYS A 182 10 0 220 80 290 A C ATOM 1284 C CYS A 182 13.521 8.880 20.989 1.00 14.28A C ANISOU 1284 C CYS A 182 1492 1609 1371 −26 9 0 A C SIGUIJ 1284 C CYSA 182 1 0 0 220 80 290 A C ATOM 1285 O CYS A 182 13.125 7.915 20.3031.00 13.79 A O ANISOU 1285 O CYS A 182 1842 1635 1379 −107 −69 22 A OSIGUIJ 1285 O CYS A 182 1 0 0 221 53 289 A O ATOM 1286 CB CYS A 18215.471 10.364 20.446 1.00 15.88 A C ANISOU 1286 CB CYS A 182 1854 19741505 −259 21 −7 A C SIGUIJ 1286 CB CYS A 182 1 0 0 220 80 290 A C ATOM1287 SG CYS A 182 17.179 10.774 20.933 1.00 16.61 A S ANISOU 1287 SG CYSA 182 1886 2331 1784 −338 −44 −111 A S SIGUIJ 1287 SG CYS A 182 1 0 0221 48 289 A S ATOM 1288 N ALA A 183 12.691 9.734 21.548 1.00 13.52 A NANISOU 1288 N ALA A 183 1501 1611 1283 3 −50 1 A N SIGUIJ 1288 N ALA A183 1 0 0 221 59 289 A N ATOM 1289 CA ALA A 183 11.260 9.592 21.273 1.0013.20 A C ANISOU 1289 CA ALA A 183 1517 1668 1319 −31 −57 −7 A C SIGUIJ1289 CA ALA A 183 1 0 0 220 80 290 A C ATOM 1290 CB ALA A 183 10.5748.603 22.227 1.00 13.34 A C ANISOU 1290 CB ALA A 183 1571 1652 1389 1 130 A C SIGUIJ 1290 CB ALA A 183 1 0 0 220 80 290 A C ATOM 1291 C ALA A183 10.599 10.959 21.446 1.00 13.39 A C ANISOU 1291 C ALA A 183 16511674 1264 −5 −1 0 A C SIGUIJ 1291 C ALA A 183 1 0 0 220 80 290 A C ATOM1292 O ALA A 183 10.937 11.736 22.383 1.00 13.25 A O ANISOU 1292 O ALA A183 1903 1675 1270 −79 −38 8 A O SIGUIJ 1292 O ALA A 183 1 0 0 221 53289 A O ATOM 1293 N GLY A 184 9.634 11.249 20.592 1.00 13.85 A N ANISOU1293 N GLY A 184 1692 1596 1308 −57 −37 11 A N SIGUIJ 1293 N GLY A 184 10 0 221 59 289 A N ATOM 1294 CA GLY A 184 8.925 12.512 20.673 1.00 14.85A C ANISOU 1294 CA GLY A 184 1833 1634 1631 4 21 0 A C SIGUIJ 1294 CAGLY A 184 1 0 0 220 79 290 A C ATOM 1295 C GLY A 184 7.853 12.524 19.5911.00 15.55 A C ANISOU 1295 C GLY A 184 1908 1981 1696 13 −48 4 A CSIGUIJ 1295 C GLY A 184 1 0 0 220 79 290 A C ATOM 1296 O GLY A 184 7.67311.534 18.865 1.00 15.41 A O ANISOU 1296 O GLY A 184 2337 1985 1746 5−160 −1 A O SIGUIJ 1296 O GLY A 184 1 0 0 221 53 289 A O ATOM 1297 N ILEA 185 7.149 13.649 19.494 1.00 16.56 A N ANISOU 1297 N ILE A 185 24642162 1717 326 −463 −226 A N SIGUIJ 1297 N ILE A 185 1 0 0 221 59 289 A NATOM 1298 CA ILE A 185 6.104 13.888 18.467 1.00 17.76 A C ANISOU 1298 CAILE A 185 2356 1838 1699 2 −403 4 A C SIGUIJ 1298 CA ILE A 185 1 0 0 22079 290 A C ATOM 1299 CB ILE A 185 4.737 14.077 19.163 1.00 18.05 A CANISOU 1299 CB ILE A 185 2558 1913 2521 8 4 0 A C SIGUIJ 1299 CB ILE A185 1 0 0 220 79 290 A C ATOM 1300 CG2 ILE A 185 3.671 14.450 18.1601.00 18.41 A C ANISOU 1300 CG2 ILE A 185 2592 2147 2532 91 −4 −3 A CSIGUIJ 1300 CG2 ILE A 185 1 0 0 220 79 290 A C ATOM 1301 CG1 ILE A 1854.303 12.782 19.873 1.00 18.24 A C ANISOU 1301 CG1 ILE A 185 2702 19372551 −42 10 −1 A C SIGUIJ 1301 CG1 ILE A 185 1 0 0 220 79 290 A C ATOM1302 CD1 ILE A 185 3.986 11.644 18.904 1.00 18.38 A C ANISOU 1302 CD1ILE A 185 2395 1924 2566 48 6 −1 A C SIGUIJ 1302 CD1 ILE A 185 1 0 0 22079 290 A C ATOM 1303 C ILE A 185 6.528 15.183 17.749 1.00 18.58 A CANISOU 1303 C ILE A 185 2666 1856 1746 −36 −310 13 A C SIGUIJ 1303 C ILEA 185 1 0 0 220 79 290 A C ATOM 1304 O ILE A 185 6.793 16.151 18.4081.00 18.04 A O ANISOU 1304 O ILE A 185 2616 1851 1719 −26 −305 5 A OSIGUIJ 1304 O ILE A 185 1 0 0 221 53 289 A O ATOM 1305 N PRO A 186 6.59715.196 16.397 1.00 19.42 A N ANISOU 1305 N PRO A 186 3006 2554 1750 −76−290 29 A N SIGUIJ 1305 N PRO A 186 1 0 0 221 59 289 A N ATOM 1306 CDPRO A 186 6.278 14.129 15.430 1.00 20.02 A C ANISOU 1306 CD PRO A 1862736 2594 1854 50 −335 −53 A C SIGUIJ 1306 CD PRO A 186 1 0 0 220 79 290A C ATOM 1307 CA PRO A 186 6.974 16.437 15.725 1.00 20.07 A C ANISOU1307 CA PRO A 186 3182 2600 1801 −148 −318 58 A C SIGUIJ 1307 CA PRO A186 1 0 0 220 79 290 A C ATOM 1308 CB PRO A 186 6.710 16.142 14.252 1.0020.37 A C ANISOU 1308 CB PRO A 186 3572 2807 1829 −63 −404 17 A C SIGUIJ1308 CB PRO A 186 1 0 0 220 79 290 A C ATOM 1309 CG PRO A 186 6.66914.734 14.124 1.00 20.70 A C ANISOU 1309 CG PRO A 186 3533 2812 1940 −80−155 12 A C SIGUIJ 1309 CG PRO A 186 1 0 0 220 79 290 A C ATOM 1310 CPRO A 186 6.142 17.609 16.194 1.00 20.31 A C ANISOU 1310 C PRO A 1863182 2629 1658 −114 −395 61 A C SIGUIJ 1310 C PRO A 186 1 0 0 220 79 290A C ATOM 1311 O PRO A 186 4.904 17.527 16.318 1.00 20.36 A O ANISOU 1311O PRO A 186 3187 2274 2361 −89 −328 31 A O SIGUIJ 1311 O PRO A 186 1 0 0221 53 289 A O ATOM 1312 N ASP A 186A 6.835 18.715 16.417 1.00 20.72 A NANISOU 1312 N ASP A 186A 2899 2555 1610 28 −240 −8 A N SIGUIJ 1312 N ASPA 186A 1 0 0 221 59 289 A N ATOM 1313 CA ASP A 186A 6.237 19.998 16.7861.00 21.18 A C ANISOU 1313 CA ASP A 186A 3476 2730 1801 334 −321 −97 A CSIGUIJ 1313 CA ASP A 186A 1 0 0 220 79 290 A C ATOM 1314 CB ASP A 186A5.366 20.539 15.625 1.00 22.27 A C ANISOU 1314 CB ASP A 186A 3473 23762017 −90 −517 40 A C SIGUIJ 1314 CB ASP A 186A 1 0 0 220 79 290 A C ATOM1315 CG ASP A 186A 6.156 20.717 14.355 1.00 23.43 A C ANISOU 1315 CG ASPA 186A 4196 5781 2219 −920 −183 −4 A C SIGUIJ 1315 CG ASP A 186A 1 0 0220 79 290 A C ATOM 1316 OD1 ASP A 186A 7.288 21.218 14.437 1.00 24.41 AO ANISOU 1316 OD1 ASP A 186A 3792 3691 2398 5 −194 −5 A O SIGUIJ 1316OD1 ASP A 186A 1 0 0 221 53 289 A O ATOM 1317 OD2 ASP A 186A 5.65320.326 13.272 1.00 24.75 A O ANISOU 1317 OD2 ASP A 186A 4673 6813 2176−1755 −103 11 A O SIGUIJ 1317 OD2 ASP A 186A 1 0 0 221 53 289 A O ATOM1318 C ASP A 186A 5.451 19.972 18.087 1.00 20.78 A C ANISOU 1318 C ASP A186A 3914 2229 1960 518 −45 −12 A C SIGUIJ 1318 C ASP A 186A 1 0 0 22079 290 A C ATOM 1319 O ASP A 186A 4.604 20.805 18.310 1.00 21.16 A OANISOU 1319 O ASP A 186A 4445 2561 3025 917 499 248 A O SIGUIJ 1319 OASP A 186A 1 0 0 221 53 289 A O ATOM 1320 N SER A 186B 5.743 18.99618.957 1.00 19.72 A N ANISOU 1320 N SER A 186B 2709 2092 2003 20 −197 −6A N SIGUIJ 1320 N SER A 186B 1 0 0 221 59 289 A N ATOM 1321 CA SER A186B 5.029 18.811 20.224 1.00 19.06 A C ANISOU 1321 CA SER A 186B 27762401 2023 −28 −167 9 A C SIGUIJ 1321 CA SER A 186B 1 0 0 220 79 290 A CATOM 1322 CB SER A 186B 4.333 17.456 20.205 1.00 18.95 A C ANISOU 1322CB SER A 186B 2800 2411 1927 −39 −165 11 A C SIGUIJ 1322 CB SER A 186B 10 0 220 78 290 A C ATOM 1323 OG SER A 186B 3.828 17.155 21.492 1.0018.85 A O ANISOU 1323 OG SER A 186B 2384 2464 1874 7 −315 30 A O SIGUIJ1323 OG SER A 186B 1 0 0 221 53 289 A O ATOM 1324 C SER A 186B 5.99418.854 21.391 1.00 18.39 A C ANISOU 1324 C SER A 186B 2588 1709 1908 5−14 0 A C SIGUIJ 1324 C SER A 186B 1 0 0 220 78 290 A C ATOM 1325 O SERA 186B 7.143 18.478 21.244 1.00 18.48 A O ANISOU 1325 O SER A 186B 26502316 1988 202 7 3 A O SIGUIJ 1325 O SER A 186B 1 0 0 221 53 289 A O ATOM1326 N ALYS A 187 5.507 19.319 22.529 0.50 17.77 A N ANISOU 1326 N ALYSA 187 2220 1630 1851 −45 −152 14 A N SIGUIJ 1326 N ALYS A 187 1 0 0 22159 289 A N ATOM 1327 N BLYS A 187 5.484 19.331 22.525 0.50 19.96 A NANISOU 1327 N BLYS A 187 2234 1592 1840 −71 −148 20 A N SIGUIJ 1327 NBLYS A 187 1 0 0 221 59 289 A N ATOM 1328 CA ALYS A 187 6.284 19.35523.760 0.50 17.28 A C ANISOU 1328 CA ALYS A 187 2079 1412 1804 −41 −68 9A C SIGUIJ 1328 CA ALYS A 187 1 0 0 220 78 290 A C ATOM 1329 CA BLYS A187 6.185 19.396 23.809 0.50 19.47 A C ANISOU 1329 CA BLYS A 187 27111446 1981 −143 −407 64 A C SIGUIJ 1329 CA BLYS A 187 1 0 0 220 78 290 AC ATOM 1330 CB ALYS A 187 5.712 20.431 24.683 0.50 18.41 A C ANISOU 1330CB ALYS A 187 2400 1530 1834 140 −77 −15 A C SIGUIJ 1330 CB ALYS A 187 10 0 220 78 290 A C ATOM 1331 CB BLYS A 187 5.424 20.327 24.777 0.5020.60 A C ANISOU 1331 CB BLYS A 187 3766 1779 2431 192 99 11 A C SIGUIJ1331 CB BLYS A 187 1 0 0 220 78 290 A C ATOM 1332 CG ALYS A 187 5.73721.819 24.058 0.50 19.76 A C ANISOU 1332 CG ALYS A 187 3743 1555 1933−99 −559 28 A C SIGUIJ 1332 CG ALYS A 187 1 0 0 220 78 290 A C ATOM 1333CG BLYS A 187 5.329 21.812 24.398 0.50 21.95 A C ANISOU 1333 CG BLYS A187 3097 1767 2428 67 −200 −8 A C SIGUIJ 1333 CG BLYS A 187 1 0 0 220 78290 A C ATOM 1334 CD ALYS A 187 5.202 22.885 25.007 0.50 21.54 A CANISOU 1334 CD ALYS A 187 6093 1801 2387 382 223 21 A C SIGUIJ 1334 CDALYS A 187 1 0 0 220 78 290 A C ATOM 1335 CD BLYS A 187 4.571 22.61425.506 0.50 23.73 A C ANISOU 1335 CD BLYS A 187 5177 3591 2541 1906 −108−75 A C SIGUIJ 1335 CD BLYS A 187 1 0 0 220 78 290 A C ATOM 1336 CE ALYSA 187 5.691 24.276 24.602 0.50 22.22 A C ANISOU 1336 CE ALYS A 187 91062124 2521 −591 519 −45 A C SIGUIJ 1336 CE ALYS A 187 1 0 0 220 78 290 AC ATOM 1337 CE BLYS A 187 4.688 24.148 25.345 0.50 24.41 A C ANISOU 1337CE BLYS A 187 13777 3655 5721 1369 1007 152 A C SIGUIJ 1337 CE BLYS A187 1 0 0 220 78 290 A C ATOM 1338 NZ ALYS A 187 5.364 25.307 25.6400.50 23.45 A N ANISOU 1338 NZ ALYS A 187 14140 2203 3005 −445 1960 −75 AN SIGUIJ 1338 NZ ALYS A 187 1 0 0 221 59 289 A N ATOM 1339 NZ BLYS A 1874.207 24.944 26.534 0.50 25.64 A N ANISOU 1339 NZ BLYS A 187 13596 39345596 1778 657 131 A N SIGUIJ 1339 NZ BLYS A 187 1 0 0 221 59 289 A NATOM 1340 C ALYS A 187 6.360 18.024 24.520 0.50 16.33 A C ANISOU 1340 CALYS A 187 1924 1408 1780 −22 1 0 A C SIGUIJ 1340 C ALYS A 187 1 0 0 22078 290 A C ATOM 1341 C BLYS A 187 6.353 18.034 24.512 0.50 18.52 A CANISOU 1341 C BLYS A 187 1939 1424 1764 −37 −3 1 A C SIGUIJ 1341 C BLYSA 187 1 0 0 220 78 290 A C ATOM 1342 O ALYS A 187 7.132 17.917 25.4800.50 16.34 A O ANISOU 1342 O ALYS A 187 1933 1749 1779 5 −3 0 A O SIGUIJ1342 O ALYS A 187 1 0 0 221 53 289 A O ATOM 1343 O BLYS A 187 7.17717.917 25.426 0.50 18.53 A O ANISOU 1343 O BLYS A 187 1942 1736 1762 0−4 0 A O SIGUIJ 1343 O BLYS A 187 1 0 0 221 53 289 A O ATOM 1344 N LYS A188 5.557 17.033 24.125 1.00 14.96 A N ANISOU 1344 N LYS A 188 1853 13631774 29 3 1 A N SIGUIJ 1344 N LYS A 188 1 0 0 221 59 289 A N ATOM 1345CA LYS A 188 5.442 15.771 24.874 1.00 14.02 A C ANISOU 1345 CA LYS A 1881589 1366 1791 10 −67 4 A C SIGUIJ 1345 CA LYS A 188 1 0 0 220 78 290 AC ATOM 1346 CB LYS A 188 4.549 14.803 24.081 1.00 14.14 A C ANISOU 1346CB LYS A 188 1573 1402 1780 −10 −36 0 A C SIGUIJ 1346 CB LYS A 188 1 0 0220 78 290 A C ATOM 1347 CG LYS A 188 3.093 15.262 24.107 1.00 14.83 A CANISOU 1347 CG LYS A 188 1593 1677 1895 69 −48 19 A C SIGUIJ 1347 CG LYSA 188 1 0 0 220 78 290 A C ATOM 1348 CD LYS A 188 2.268 14.487 23.1181.00 16.07 A C ANISOU 1348 CD LYS A 188 1835 1920 2045 −56 −162 −51 A CSIGUIJ 1348 CD LYS A 188 1 0 0 220 78 290 A C ATOM 1349 CE LYS A 1880.771 14.891 23.168 1.00 16.84 A C ANISOU 1349 CE LYS A 188 1864 23022691 47 −123 10 A C SIGUIJ 1349 CE LYS A 188 1 0 0 220 78 290 A C ATOM1350 NZ LYS A 188 0.149 14.611 24.457 1.00 18.97 A N ANISOU 1350 NZ LYSA 188 2285 2681 2766 −116 36 9 A N SIGUIJ 1350 NZ LYS A 188 1 0 0 221 59289 A N ATOM 1351 C LYS A 188 6.825 15.159 25.109 1.00 13.21 A C ANISOU1351 C LYS A 188 1592 1396 1314 28 3 0 A C SIGUIJ 1351 C LYS A 188 1 0 0220 77 290 A C ATOM 1352 O LYS A 188 7.611 14.950 24.182 1.00 12.89 A OANISOU 1352 O LYS A 188 1598 1827 1295 135 −25 −1 A O SIGUIJ 1352 O LYSA 188 1 0 0 221 53 289 A O ATOM 1353 N ASN A 189 7.106 14.821 26.3601.00 12.05 A N ANISOU 1353 N ASN A 189 1493 1287 1305 −33 15 −2 A NSIGUIJ 1353 N ASN A 189 1 0 0 221 59 289 A N ATOM 1354 CA ASN A 1898.442 14.336 26.726 1.00 11.64 A C ANISOU 1354 CA ASN A 189 1506 12901360 −27 −13 2 A C SIGUIJ 1354 CA ASN A 189 1 0 0 220 77 290 A C ATOM1355 CB ASN A 189 9.451 15.474 26.529 1.00 11.73 A C ANISOU 1355 CB ASNA 189 1504 1272 1391 −11 −9 1 A C SIGUIJ 1355 CB ASN A 189 1 0 0 220 77290 A C ATOM 1356 CG ASN A 189 10.808 15.004 26.122 1.00 12.45 A CANISOU 1356 CG ASN A 189 1520 1412 1302 30 −41 −8 A C SIGUIJ 1356 CG ASNA 189 1 0 0 220 77 290 A C ATOM 1357 OD1 ASN A 189 11.230 13.842 26.3581.00 11.93 A O ANISOU 1357 OD1 ASN A 189 1572 1450 1292 100 121 51 A OSIGUIJ 1357 OD1 ASN A 189 1 0 0 221 53 289 A O ATOM 1358 ND2 ASN A 18911.548 15.934 25.501 1.00 13.28 A N ANISOU 1358 ND2 ASN A 189 1956 14911618 −105 270 −58 A N SIGUIJ 1358 ND2 ASN A 189 1 0 0 221 59 289 A NATOM 1359 C ASN A 189 8.442 13.848 28.184 1.00 11.46 A C ANISOU 1359 CASN A 189 1489 1279 1365 57 8 3 A C SIGUIJ 1359 C ASN A 189 1 0 0 220 77290 A C ATOM 1360 O ASN A 189 7.460 14.017 28.885 1.00 11.18 A O ANISOU1360 O ASN A 189 1475 1295 1383 83 3 2 A O SIGUIJ 1360 O ASN A 189 1 0 0221 53 289 A O ATOM 1361 N ALA A 190 9.588 13.320 28.631 1.00 11.38 A NANISOU 1361 N ALA A 190 1480 1239 1397 41 −4 −1 A N SIGUIJ 1361 N ALA A190 1 0 0 221 59 289 A N ATOM 1362 CA ALA A 190 9.839 13.028 30.026 1.0011.34 A C ANISOU 1362 CA ALA A 190 1428 1218 1403 114 4 6 A C SIGUIJ1362 CA ALA A 190 1 0 0 220 77 290 A C ATOM 1363 CB ALA A 190 10.69511.762 30.129 1.00 11.42 A C ANISOU 1363 CB ALA A 190 1576 1290 1506 2206 7 A C SIGUIJ 1363 CB ALA A 190 1 0 0 220 77 290 A C ATOM 1364 C ALA A190 10.590 14.233 30.624 1.00 11.69 A C ANISOU 1364 C ALA A 190 14471216 1552 114 −8 4 A C SIGUIJ 1364 C ALA A 190 1 0 0 220 77 290 A C ATOM1365 O ALA A 190 11.000 15.193 29.874 1.00 12.39 A O ANISOU 1365 O ALA A190 1837 1276 1616 5 44 2 A O SIGUIJ 1365 O ALA A 190 1 0 0 221 53 289 AO ATOM 1366 N CYS A 191 10.750 14.233 31.946 1.00 11.81 A N ANISOU 1366N CYS A 191 1490 1103 1564 9 2 0 A N SIGUIJ 1366 N CYS A 191 1 0 0 22159 289 A N ATOM 1367 CA CYS A 191 11.495 15.320 32.611 1.00 11.91 A CANISOU 1367 CA CYS A 191 1544 1111 1703 −2 −39 −5 A C SIGUIJ 1367 CA CYSA 191 1 0 0 220 77 290 A C ATOM 1368 C CYS A 191 12.036 14.793 33.9441.00 11.80 A C ANISOU 1368 C CYS A 191 1214 1167 1666 0 100 4 A C SIGUIJ1368 C CYS A 191 1 0 0 220 77 290 A C ATOM 1369 O CYS A 191 12.04013.570 34.192 1.00 11.71 A O ANISOU 1369 O CYS A 191 1357 1171 1607 −38−73 0 A O SIGUIJ 1369 O CYS A 191 1 0 0 221 53 289 A O ATOM 1370 CB CYSA 191 10.575 16.562 32.752 1.00 12.54 A C ANISOU 1370 CB CYS A 191 17301191 2157 120 41 −2 A C SIGUIJ 1370 CB CYS A 191 1 0 0 220 77 290 A CATOM 1371 SG CYS A 191 11.386 18.128 33.252 1.00 13.85 A S ANISOU 1371SG CYS A 191 1970 1270 1902 −56 194 24 A S SIGUIJ 1371 SG CYS A 191 1 00 221 48 289 A S ATOM 1372 N AASN A 192 12.570 15.687 34.798 0.50 11.82A N ANISOU 1372 N AASN A 192 1408 1193 1734 −56 26 −1 A N SIGUIJ 1372 NAASN A 192 1 0 0 221 59 289 A N ATOM 1373 N BASN A 192 12.568 15.69634.795 0.50 14.01 A N ANISOU 1373 N BASN A 192 1391 1189 1728 −42 28 −1A N SIGUIJ 1373 N BASN A 192 1 0 0 221 59 289 A N ATOM 1374 CA AASN A192 13.201 15.266 36.067 0.50 12.62 A C ANISOU 1374 CA AASN A 192 14201257 1736 20 48 5 A C SIGUIJ 1374 CA AASN A 192 1 0 0 220 77 290 A CATOM 1375 CA BASN A 192 13.225 15.299 36.063 0.50 14.81 A C ANISOU 1375CA BASN A 192 1374 1279 1725 12 59 5 A C SIGUIJ 1375 CA BASN A 192 1 0 0220 77 290 A C ATOM 1376 CB AASN A 192 13.672 16.443 36.931 0.50 15.37 AC ANISOU 1376 CB AASN A 192 2253 1352 1788 −236 −36 13 A C SIGUIJ 1376CB AASN A 192 1 0 0 220 77 290 A C ATOM 1377 CB BASN A 192 13.644 16.49436.969 0.50 17.56 A C ANISOU 1377 CB BASN A 192 6809 1617 1888 −1290−736 178 A C SIGUIJ 1377 CB BASN A 192 1 0 0 220 77 290 A C ATOM 1378 CGAASN A 192 14.769 17.215 36.280 0.50 17.74 A C ANISOU 1378 CG AASN A 1922339 1369 1933 −271 65 −28 A C SIGUIJ 1378 CG AASN A 192 1 0 0 220 77290 A C ATOM 1379 CG BASN A 192 13.934 17.777 36.193 0.50 19.93 A CANISOU 1379 CG BASN A 192 3989 1283 1874 −239 −50 5 A C SIGUIJ 1379 CGBASN A 192 1 0 0 220 77 290 A C ATOM 1380 OD1 AASN A 192 14.522 18.10635.442 0.50 19.81 A O ANISOU 1380 OD1 AASN A 192 3003 1423 2051 −256−107 24 A O SIGUIJ 1380 OD1 AASN A 192 1 0 0 221 53 289 A O ATOM 1381OD1 BASN A 192 15.078 18.232 36.121 0.50 22.00 A O ANISOU 1381 OD1 BASNA 192 4514 4570 2567 −1549 5 −5 A O SIGUIJ 1381 OD1 BASN A 192 1 0 0 22153 289 A O ATOM 1382 ND2 AASN A 192 16.007 16.879 36.631 0.50 19.13 A NANISOU 1382 ND2 AASN A 192 2368 1614 2078 −206 19 −9 A N SIGUIJ 1382 ND2AASN A 192 1 0 0 221 59 289 A N ATOM 1383 ND2 BASN A 192 12.905 18.35535.601 0.50 21.32 A N ANISOU 1383 ND2 BASN A 192 4270 1309 2842 −265−567 76 A N SIGUIJ 1383 ND2 BASN A 192 1 0 0 221 59 289 A N ATOM 1384 CAASN A 192 12.264 14.462 36.903 0.50 11.77 A C ANISOU 1384 C AASN A 1921267 1262 1531 −1 −132 −5 A C SIGUIJ 1384 C AASN A 192 1 0 0 220 77 290A C ATOM 1385 C BASN A 192 12.277 14.470 36.887 0.50 13.96 A C ANISOU1385 C BASN A 192 1223 1263 1484 −7 −135 −8 A C SIGUIJ 1385 C BASN A 1921 0 0 220 77 290 A C ATOM 1386 O AASN A 192 11.125 14.863 37.169 0.5012.07 A O ANISOU 1386 O AASN A 192 1291 1266 1846 0 −49 0 A O SIGUIJ1386 O AASN A 192 1 0 0 221 53 289 A O ATOM 1387 O BASN A 192 11.13014.866 37.118 0.50 14.26 A O ANISOU 1387 O BASN A 192 1248 1266 1997 1−23 1 A O SIGUIJ 1387 O BASN A 192 1 0 0 221 53 289 A O ATOM 1388 N GLYA 193 12.808 13.370 37.406 1.00 10.39 A N ANISOU 1388 N GLY A 193 11441264 1345 17 6 −1 A N SIGUIJ 1388 N GLY A 193 1 0 0 221 59 289 A N ATOM1389 CA GLY A 193 12.005 12.434 38.185 1.00 10.12 A C ANISOU 1389 CA GLYA 193 1149 1288 1295 −17 −30 −4 A C SIGUIJ 1389 CA GLY A 193 1 0 0 22077 290 A C ATOM 1390 C GLY A 193 11.536 11.260 37.368 1.00 9.29 A CANISOU 1390 C GLY A 193 966 1257 1264 63 −38 8 A C SIGUIJ 1390 C GLY A193 1 0 0 220 76 290 A C ATOM 1391 O GLY A 193 11.109 10.228 37.949 1.0010.02 A O ANISOU 1391 O GLY A 193 1252 1299 1302 −7 1 0 A O SIGUIJ 1391O GLY A 193 1 0 0 221 53 289 A O ATOM 1392 N ASP A 194 11.609 11.35536.050 1.00 8.82 A N ANISOU 1392 N ASP A 194 1051 990 1255 2 −37 −1 A NSIGUIJ 1392 N ASP A 194 1 0 0 221 59 289 A N ATOM 1393 CA ASP A 19411.158 10.267 35.167 1.00 9.00 A C ANISOU 1393 CA ASP A 194 1094 9921236 −24 −6 0 A C SIGUIJ 1393 CA ASP A 194 1 0 0 220 76 290 A C ATOM1394 CB ASP A 194 10.554 10.842 33.894 1.00 9.29 A C ANISOU 1394 CB ASPA 194 1159 1027 1245 22 −6 0 A C SIGUIJ 1394 CB ASP A 194 1 0 0 220 76290 A C ATOM 1395 CG ASP A 194 9.250 11.547 34.130 1.00 9.46 A C ANISOU1395 CG ASP A 194 1171 1042 1269 32 −1 0 A C SIGUIJ 1395 CG ASP A 194 10 0 220 76 290 A C ATOM 1396 OD1 ASP A 194 8.417 11.087 34.969 1.00 9.59A O ANISOU 1396 OD1 ASP A 194 1226 1150 1278 −16 4 0 A O SIGUIJ 1396 OD1ASP A 194 1 0 0 221 53 289 A O ATOM 1397 OD2 ASP A 194 8.990 12.56633.432 1.00 10.06 A O ANISOU 1397 OD2 ASP A 194 1204 1058 1309 52 −5 1 AO SIGUIJ 1397 OD2 ASP A 194 1 0 0 221 53 289 A O ATOM 1398 C ASP A 19412.265 9.291 34.827 1.00 8.95 A C ANISOU 1398 C ASP A 194 1115 1025 11812 0 0 A C SIGUIJ 1398 C ASP A 194 1 0 0 220 76 290 A C ATOM 1399 O ASP A194 11.930 8.200 34.314 1.00 9.47 A O ANISOU 1399 O ASP A 194 1291 10421204 −33 −10 2 A O SIGUIJ 1399 O ASP A 194 1 0 0 221 52 289 A O ATOM1400 N SER A 195 13.524 9.644 35.045 1.00 8.61 A N ANISOU 1400 N SER A195 1112 1039 1117 1 0 0 A N SIGUIJ 1400 N SER A 195 1 0 0 221 59 289 AN ATOM 1401 CA SER A 195 14.636 8.728 34.715 1.00 9.06 A C ANISOU 1401CA SER A 195 1108 1034 1200 −7 15 0 A C SIGUIJ 1401 CA SER A 195 1 0 0220 76 290 A C ATOM 1402 CB SER A 195 15.932 9.226 35.339 1.00 9.26 A CANISOU 1402 CB SER A 195 1129 1029 1310 −11 −23 1 A C SIGUIJ 1402 CB SERA 195 1 0 0 220 76 290 A C ATOM 1403 OG SER A 195 16.952 8.239 35.2581.00 10.77 A O ANISOU 1403 OG SER A 195 1251 1131 1836 94 34 5 A OSIGUIJ 1403 OG SER A 195 1 0 0 221 52 289 A O ATOM 1404 C SER A 19514.390 7.331 35.236 1.00 8.79 A C ANISOU 1404 C SER A 195 1093 1037 11355 −1 0 A C SIGUIJ 1404 C SER A 195 1 0 0 220 76 290 A C ATOM 1405 O SERA 195 13.928 7.140 36.359 1.00 8.77 A O ANISOU 1405 O SER A 195 11411165 1125 0 0 0 A O SIGUIJ 1405 O SER A 195 1 0 0 221 52 289 A O ATOM1406 N GLY A 196 14.731 6.344 34.397 1.00 8.96 A N ANISOU 1406 N GLY A196 1083 1037 1172 8 3 0 A N SIGUIJ 1406 N GLY A 196 1 0 0 221 59 289 AN ATOM 1407 CA GLY A 196 14.603 4.955 34.824 1.00 9.79 A C ANISOU 1407CA GLY A 196 1346 1045 1251 −26 5 −1 A C SIGUIJ 1407 CA GLY A 196 1 0 0220 76 290 A C ATOM 1408 C GLY A 196 13.268 4.335 34.559 1.00 10.15 A CANISOU 1408 C GLY A 196 1357 1133 1279 −59 3 −2 A C SIGUIJ 1408 C GLY A196 1 0 0 220 76 290 A C ATOM 1409 O GLY A 196 13.122 3.077 34.625 1.0011.37 A O ANISOU 1409 O GLY A 196 1574 1138 1455 −86 12 −5 A O SIGUIJ1409 O GLY A 196 1 0 0 221 52 289 A O ATOM 1410 N GLY A 197 12.270 5.17434.293 1.00 10.34 A N ANISOU 1410 N GLY A 197 1390 1225 1252 3 0 0 A NSIGUIJ 1410 N GLY A 197 1 0 0 221 59 289 A N ATOM 1411 CA GLY A 19710.950 4.639 34.022 1.00 10.70 A C ANISOU 1411 CA GLY A 197 1399 12581271 −14 −5 1 A C SIGUIJ 1411 CA GLY A 197 1 0 0 220 76 290 A C ATOM1412 C GLY A 197 10.775 4.179 32.572 1.00 10.49 A C ANISOU 1412 C GLY A197 1284 1160 1264 32 0 0 A C SIGUIJ 1412 C GLY A 197 1 0 0 220 76 290 AC ATOM 1413 O GLY A 197 11.628 4.364 31.687 1.00 10.72 A O ANISOU 1413 OGLY A 197 1301 1386 1252 −6 3 0 A O SIGUIJ 1413 O GLY A 197 1 0 0 221 52289 A O ATOM 1414 N PRO A 198 9.659 3.487 32.333 1.00 10.32 A N ANISOU1414 N PRO A 198 1299 1211 1147 −4 22 −1 A N SIGUIJ 1414 N PRO A 198 1 00 221 59 289 A N ATOM 1415 CD PRO A 198 8.577 3.242 33.332 1.00 10.54 AC ANISOU 1415 CD PRO A 198 1332 1247 1182 2 56 1 A C SIGUIJ 1415 CD PROA 198 1 0 0 220 76 290 A C ATOM 1416 CA PRO A 198 9.493 2.681 31.1151.00 10.29 A C ANISOU 1416 CA PRO A 198 1438 1205 1158 36 −19 −3 A CSIGUIJ 1416 CA PRO A 198 1 0 0 220 76 290 A C ATOM 1417 CB PRO A 1988.462 1.655 31.568 1.00 10.41 A C ANISOU 1417 CB PRO A 198 1537 12781330 −35 48 −7 A C SIGUIJ 1417 CB PRO A 198 1 0 0 220 76 290 A C ATOM1418 CG PRO A 198 7.644 2.375 32.586 1.00 11.03 A C ANISOU 1418 CG PRO A198 1439 1279 1276 −34 −28 6 A C SIGUIJ 1418 CG PRO A 198 1 0 0 220 76290 A C ATOM 1419 C PRO A 198 8.957 3.456 29.895 1.00 10.64 A C ANISOU1419 C PRO A 198 1350 1170 1163 −39 −14 3 A C SIGUIJ 1419 C PRO A 198 10 0 220 76 290 A C ATOM 1420 O PRO A 198 8.036 4.276 30.000 1.00 11.03 AO ANISOU 1420 O PRO A 198 1485 1332 1335 93 −2 −1 A O SIGUIJ 1420 O PROA 198 1 0 0 221 52 289 A O ATOM 1421 N LEU A 199 9.511 3.089 28.732 1.0010.69 A N ANISOU 1421 N LEU A 199 1373 1162 1185 −100 27 −12 A N SIGUIJ1421 N LEU A 199 1 0 0 221 59 289 A N ATOM 1422 CA LEU A 199 8.960 3.41627.418 1.00 10.99 A C ANISOU 1422 CA LEU A 199 1462 1258 1196 −28 12 −1A C SIGUIJ 1422 CA LEU A 199 1 0 0 220 76 290 A C ATOM 1423 CB LEU A 19910.064 4.001 26.536 1.00 11.16 A C ANISOU 1423 CB LEU A 199 1531 13571204 −105 38 −15 A C SIGUIJ 1423 CB LEU A 199 1 0 0 220 76 290 A C ATOM1424 CG LEU A 199 9.679 4.334 25.092 1.00 11.53 A C ANISOU 1424 CG LEU A199 1678 1387 1215 −188 −4 2 A C SIGUIJ 1424 CG LEU A 199 1 0 0 220 76290 A C ATOM 1425 CD1 LEU A 199 8.681 5.517 25.023 1.00 12.70 A C ANISOU1425 CD1 LEU A 199 1922 1558 2204 14 −71 6 A C SIGUIJ 1425 CD1 LEU A 1991 0 0 220 76 290 A C ATOM 1426 CD2 LEU A 199 10.953 4.704 24.328 1.0012.64 A C ANISOU 1426 CD2 LEU A 199 1876 3221 1286 −740 46 −32 A CSIGUIJ 1426 CD2 LEU A 199 1 0 0 220 75 290 A C ATOM 1427 C LEU A 1998.489 2.055 26.870 1.00 11.49 A C ANISOU 1427 C LEU A 199 1340 1248 127014 8 1 A C SIGUIJ 1427 C LEU A 199 1 0 0 220 75 290 A C ATOM 1428 O LEUA 199 9.287 1.147 26.665 1.00 11.40 A O ANISOU 1428 O LEU A 199 13391245 1380 3 −3 0 A O SIGUIJ 1428 O LEU A 199 1 0 0 221 52 289 A O ATOM1429 N AVAL A 200 7.185 1.905 26.707 0.50 11.93 A N ANISOU 1429 N AVAL A200 1338 1137 1409 16 −1 0 A N SIGUIJ 1429 N AVAL A 200 1 0 0 221 59 289A N ATOM 1430 N BVAL A 200 7.186 1.915 26.680 0.50 14.12 A N ANISOU 1430N BVAL A 200 1344 1287 1383 6 0 0 A N SIGUIJ 1430 N BVAL A 200 1 0 0 22159 289 A N ATOM 1431 CA AVAL A 200 6.624 0.630 26.281 0.50 13.23 A CANISOU 1431 CA AVAL A 200 1574 1180 1391 −88 −36 12 A C SIGUIJ 1431 CAAVAL A 200 1 0 0 220 75 290 A C ATOM 1432 CA BVAL A 200 6.581 0.63926.300 0.50 15.42 A C ANISOU 1432 CA BVAL A 200 1642 1338 1400 −117 −5623 A C SIGUIJ 1432 CA BVAL A 200 1 0 0 220 75 290 A C ATOM 1433 CB AVALA 200 5.606 0.099 27.295 0.50 13.34 A C ANISOU 1433 CB AVAL A 200 16721757 1391 −334 −62 70 A C SIGUIJ 1433 CB AVAL A 200 1 0 0 220 75 290 A CATOM 1434 CB BVAL A 200 5.488 0.249 27.312 0.50 15.53 A C ANISOU 1434 CBBVAL A 200 1838 1626 1527 −304 82 −66 A C SIGUIJ 1434 CB BVAL A 200 1 00 220 75 290 A C ATOM 1435 CG1 AVAL A 200 6.292 −0.162 28.632 0.50 13.55A C ANISOU 1435 CG1 AVAL A 200 1665 2286 1342 11 5 0 A C SIGUIJ 1435 CG1AVAL A 200 1 0 0 220 75 290 A C ATOM 1436 CG1 BVAL A 200 4.723 −1.01726.843 0.50 15.74 A C ANISOU 1436 CG1 BVAL A 200 1410 1412 1576 0 −6 0 AC SIGUIJ 1436 CG1 BVAL A 200 1 0 0 220 75 290 A C ATOM 1437 CG2 AVAL A200 4.463 1.047 27.461 0.50 14.98 A C ANISOU 1437 CG2 AVAL A 200 19412131 2307 −33 27 3 A C SIGUIJ 1437 CG2 AVAL A 200 1 0 0 220 75 290 A CATOM 1438 CG2 BVAL A 200 6.135 −0.022 28.679 0.50 17.17 A C ANISOU 1438CG2 BVAL A 200 2144 2640 1587 −35 −16 0 A C SIGUIJ 1438 CG2 BVAL A 200 10 0 220 75 290 A C ATOM 1439 C AVAL A 200 5.981 0.752 24.908 0.50 14.07A C ANISOU 1439 C AVAL A 200 1498 1485 1367 0 3 0 A C SIGUIJ 1439 C AVALA 200 1 0 0 220 75 290 A C ATOM 1440 C BVAL A 200 5.987 0.762 24.8970.50 16.26 A C ANISOU 1440 C BVAL A 200 1490 1495 1371 0 0 0 A C SIGUIJ1440 C BVAL A 200 1 0 0 220 75 290 A C ATOM 1441 O AVAL A 200 5.3051.741 24.594 0.50 13.73 A O ANISOU 1441 O AVAL A 200 1646 1522 1422 72−118 −42 A O SIGUIJ 1441 O AVAL A 200 1 0 0 221 52 289 A O ATOM 1442 OBVAL A 200 5.352 1.768 24.551 0.50 15.92 A O ANISOU 1442 O BVAL A 2002287 1656 1640 355 −485 −204 A O SIGUIJ 1442 O BVAL A 200 1 0 0 221 52289 A O ATOM 1443 N CYS A 201 6.224 −0.256 24.071 0.50 15.72 A N ANISOU1443 N CYS A 201 1271 1472 1352 −39 −2 −1 A N SIGUIJ 1443 N CYS A 201 10 0 221 59 289 A N ATOM 1444 CA CYS A 201 5.658 −0.276 22.719 1.00 17.44A C ANISOU 1444 CA CYS A 201 2518 2148 1573 12 −528 −6 A C SIGUIJ 1444CA CYS A 201 1 0 0 220 75 290 A C ATOM 1445 C CYS A 201 5.110 −1.67122.498 1.00 18.94 A C ANISOU 1445 C CYS A 201 2602 2150 2126 10 −638 −32A C SIGUIJ 1445 C CYS A 201 1 0 0 220 75 290 A C ATOM 1446 O CYS A 2015.813 −2.658 22.695 1.00 19.18 A O ANISOU 1446 O CYS A 201 4095 25832869 839 −1856 −746 A O SIGUIJ 1446 O CYS A 201 1 0 0 221 52 289 A OATOM 1447 CB CYS A 201 6.748 −0.005 21.674 1.00 17.59 A C ANISOU 1447 CBCYS A 201 3256 3970 2261 −353 139 22 A C SIGUIJ 1447 CB CYS A 201 1 0 0220 75 290 A C ATOM 1448 SG CYS A 201 7.974 1.255 22.085 1.00 17.50 A SANISOU 1448 SG CYS A 201 2224 2944 1746 673 162 133 A S SIGUIJ 1448 SGCYS A 201 1 0 0 221 48 289 A S ATOM 1449 N ARG A 202 3.867 −1.771 22.0561.00 20.47 A N ANISOU 1449 N ARG A 202 2697 3430 2998 −9 −918 −237 A NSIGUIJ 1449 N ARG A 202 1 0 0 221 59 289 A N ATOM 1450 CA ARG A 2023.429 −3.048 21.476 1.00 21.98 A C ANISOU 1450 CA ARG A 202 3505 35462423 −510 −422 −111 A C SIGUIJ 1450 CA ARG A 202 1 0 0 220 75 290 A CATOM 1451 CB ARG A 202 4.356 −3.484 20.322 1.00 23.51 A C ANISOU 1451 CBARG A 202 4708 4464 3162 −225 458 −188 A C SIGUIJ 1451 CB ARG A 202 1 00 220 75 290 A C ATOM 1452 CG ARG A 202 4.054 −2.872 18.967 1.00 25.72 AC ANISOU 1452 CG ARG A 202 6650 4820 3356 −316 −15 2 A C SIGUIJ 1452 CGARG A 202 1 0 0 220 75 290 A C ATOM 1453 CD ARG A 202 4.130 −3.98117.913 1.00 27.39 A C ANISOU 1453 CD ARG A 202 15836 5050 3417 1325−1073 −124 A C SIGUIJ 1453 CD ARG A 202 1 0 0 220 75 290 A C ATOM 1454NE ARG A 202 3.147 −5.039 18.198 1.00 28.89 A N ANISOU 1454 NE ARG A 20219882 7865 11675 −1772 1472 −268 A N SIGUIJ 1454 NE ARG A 202 1 0 0 22159 289 A N ATOM 1455 CZ ARG A 202 3.241 −6.309 17.802 1.00 29.52 A CANISOU 1455 CZ ARG A 202 13635 7753 10102 −1680 −267 98 A C SIGUIJ 1455CZ ARG A 202 1 0 0 220 75 290 A C ATOM 1456 NH1 ARG A 202 4.279 −6.72217.087 1.00 30.11 A N ANISOU 1456 NH1 ARG A 202 14569 12497 10591 146 302 A N SIGUIJ 1456 NH1 ARG A 202 1 0 0 221 59 289 A N ATOM 1457 NH2 ARG A202 2.286 −7.177 18.134 1.00 30.19 A N ANISOU 1457 NH2 ARG A 202 142208203 10911 −2155 176 −83 A N SIGUIJ 1457 NH2 ARG A 202 1 0 0 221 59 289A N ATOM 1458 C ARG A 202 3.527 −4.078 22.596 1.00 21.91 A C ANISOU 1458C ARG A 202 3709 3701 2523 −1 22 −1 A C SIGUIJ 1458 C ARG A 202 1 0 0220 75 290 A C ATOM 1459 O ARG A 202 3.882 −5.252 22.360 1.00 22.61 A OANISOU 1459 O ARG A 202 4400 3923 2787 459 −1263 −433 A O SIGUIJ 1459 OARG A 202 1 0 0 221 52 289 A O ATOM 1460 N GLY A 207 3.247 −3.629 23.8161.00 21.43 A N ANISOU 1460 N GLY A 207 2943 3658 2516 −77 −115 −13 A NSIGUIJ 1460 N GLY A 207 1 0 0 221 59 289 A N ATOM 1461 CA GLY A 2073.230 −4.550 24.940 1.00 20.55 A C ANISOU 1461 CA GLY A 207 2370 36772563 54 −17 4 A C SIGUIJ 1461 CA GLY A 207 1 0 0 220 75 290 A C ATOM1462 C GLY A 207 4.528 −4.917 25.648 1.00 19.61 A C ANISOU 1462 C GLY A207 2269 2796 2561 −214 25 13 A C SIGUIJ 1462 C GLY A 207 1 0 0 220 74290 A C ATOM 1463 O GLY A 207 4.524 −5.662 26.630 1.00 20.31 A O ANISOU1463 O GLY A 207 3111 2799 2580 −291 −10 6 A O SIGUIJ 1463 O GLY A 207 10 0 221 52 289 A O ATOM 1464 N THR A 208 5.648 −4.397 25.155 1.00 18.38A N ANISOU 1464 N THR A 208 2147 2379 2325 −38 −69 −12 A N SIGUIJ 1464 NTHR A 208 1 0 0 221 59 289 A N ATOM 1465 CA THR A 208 6.940 −4.76425.704 1.00 17.05 A C ANISOU 1465 CA THR A 208 2120 1671 2223 −212 −84−107 A C SIGUIJ 1465 CA THR A 208 1 0 0 220 74 290 A C ATOM 1466 CB THRA 208 7.852 −5.662 24.730 1.00 17.59 A C ANISOU 1466 CB THR A 208 23261668 2241 −148 21 −19 A C SIGUIJ 1466 CB THR A 208 1 0 0 220 74 290 A CATOM 1467 OG1 THR A 208 8.404 −4.889 23.624 1.00 18.78 A O ANISOU 1467OG1 THR A 208 2979 2205 2256 −732 −64 49 A O SIGUIJ 1467 OG1 THR A 208 10 0 221 52 289 A O ATOM 1468 CG2 THR A 208 7.041 −6.852 24.228 1.0018.33 A C ANISOU 1468 CG2 THR A 208 3837 2352 2244 −1168 −3 2 A C SIGUIJ1468 CG2 THR A 208 1 0 0 220 74 290 A C ATOM 1469 C THR A 208 7.712−3.509 26.076 1.00 15.64 A C ANISOU 1469 C THR A 208 1738 1537 1589 −3137 −6 A C SIGUIJ 1469 C THR A 208 1 0 0 220 74 290 A C ATOM 1470 O THR A208 7.567 −2.413 25.438 1.00 15.24 A O ANISOU 1470 O THR A 208 1892 15441644 −30 −22 2 A O SIGUIJ 1470 O THR A 208 1 0 0 221 52 289 A O ATOM1471 N LEU A 209 8.579 −3.704 27.046 1.00 14.47 A N ANISOU 1471 N LEU A209 1766 1283 1616 −84 −5 2 A N SIGUIJ 1471 N LEU A 209 1 0 0 221 59 289A N ATOM 1472 CA LEU A 209 9.498 −2.670 27.440 1.00 13.39 A C ANISOU1472 CA LEU A 209 1771 1353 1409 −147 84 −29 A C SIGUIJ 1472 CA LEU A209 1 0 0 220 74 290 A C ATOM 1473 CB LEU A 209 10.155 −3.066 28.7761.00 13.02 A C ANISOU 1473 CB LEU A 209 1714 1258 1427 −240 60 −34 A CSIGUIJ 1473 CB LEU A 209 1 0 0 220 74 290 A C ATOM 1474 CG LEU A 20911.113 −1.980 29.356 1.00 12.58 A C ANISOU 1474 CG LEU A 209 1662 12141564 −188 7 −7 A C SIGUIJ 1474 CG LEU A 209 1 0 0 220 74 290 A C ATOM1475 CD1 LEU A 209 10.365 −0.768 29.797 1.00 13.15 A C ANISOU 1475 CD1LEU A 209 1871 1300 1615 −55 −1 0 A C SIGUIJ 1475 CD1 LEU A 209 1 0 0220 74 290 A C ATOM 1476 CD2 LEU A 209 11.874 −2.570 30.495 1.00 13.63 AC ANISOU 1476 CD2 LEU A 209 1888 1584 1588 67 −12 −3 A C SIGUIJ 1476 CD2LEU A 209 1 0 0 220 74 290 A C ATOM 1477 C LEU A 209 10.546 −2.45326.352 1.00 13.39 A C ANISOU 1477 C LEU A 209 1684 1215 1320 −96 −3 1 AC SIGUIJ 1477 C LEU A 209 1 0 0 220 74 290 A C ATOM 1478 O LEU A 20911.313 −3.377 26.034 1.00 14.33 A O ANISOU 1478 O LEU A 209 2821 16432129 572 764 342 A O SIGUIJ 1478 O LEU A 209 1 0 0 221 52 289 A O ATOM1479 N GLN A 210 10.630 −1.241 25.805 1.00 11.99 A N ANISOU 1479 N GLN A210 1456 1205 1300 −81 −2 1 A N SIGUIJ 1479 N GLN A 210 1 0 0 221 58 289A N ATOM 1480 CA GLN A 210 11.629 −0.966 24.792 1.00 11.62 A C ANISOU1480 CA GLN A 210 1468 1260 1294 −94 4 −2 A C SIGUIJ 1480 CA GLN A 210 10 0 220 74 290 A C ATOM 1481 CB GLN A 210 10.930 −0.471 23.528 1.0011.73 A C ANISOU 1481 CB GLN A 210 1575 1458 1287 36 2 0 A C SIGUIJ 1481CB GLN A 210 1 0 0 220 74 290 A C ATOM 1482 CG GLN A 210 10.167 −1.57622.767 1.00 11.87 A C ANISOU 1482 CG GLN A 210 1685 1521 1267 −58 34 −8A C SIGUIJ 1482 CG GLN A 210 1 0 0 220 74 290 A C ATOM 1483 CD GLN A 21011.077 −2.553 22.089 1.00 12.65 A C ANISOU 1483 CD GLN A 210 1734 15941166 31 −32 −4 A C SIGUIJ 1483 CD GLN A 210 1 0 0 220 74 290 A C ATOM1484 OE1 GLN A 210 12.101 −2.185 21.526 1.00 12.72 A O ANISOU 1484 OE1GLN A 210 1845 1744 1420 −28 121 −21 A O SIGUIJ 1484 OE1 GLN A 210 1 0 0221 52 289 A O ATOM 1485 NE2 GLN A 210 10.699 −3.842 22.095 1.00 13.51 AN ANISOU 1485 NE2 GLN A 210 2158 1625 1824 −102 6 −1 A N SIGUIJ 1485 NE2GLN A 210 1 0 0 221 58 289 A N ATOM 1486 C GLN A 210 12.663 0.084 25.2281.00 11.48 A C ANISOU 1486 C GLN A 210 1409 1202 1310 −29 −4 1 A CSIGUIJ 1486 C GLN A 210 1 0 0 220 74 290 A C ATOM 1487 O GLN A 21013.757 0.110 24.704 1.00 11.76 A O ANISOU 1487 O GLN A 210 1424 15331356 −12 16 −1 A O SIGUIJ 1487 O GLN A 210 1 0 0 221 52 289 A O ATOM1488 N GLY A 211 12.322 0.947 26.191 1.00 11.15 A N ANISOU 1488 N GLY A211 1398 1218 1310 −28 −8 2 A N SIGUIJ 1488 N GLY A 211 1 0 0 221 58 289A N ATOM 1489 CA GLY A 211 13.247 1.980 26.650 1.00 11.16 A C ANISOU1489 CA GLY A 211 1547 1392 1244 −207 55 −38 A C SIGUIJ 1489 CA GLY A211 1 0 0 220 74 290 A C ATOM 1490 C GLY A 211 13.133 2.227 28.125 1.0010.56 A C ANISOU 1490 C GLY A 211 1286 1259 1228 0 1 0 A C SIGUIJ 1490 CGLY A 211 1 0 0 220 74 290 A C ATOM 1491 O GLY A 211 12.113 1.957 28.7791.00 10.95 A O ANISOU 1491 O GLY A 211 1278 1367 1229 −25 0 0 A O SIGUIJ1491 O GLY A 211 1 0 0 221 52 289 A O ATOM 1492 N LEU A 212 14.212 2.79328.658 1.00 10.43 A N ANISOU 1492 N LEU A 212 1263 1140 1161 56 13 6 A NSIGUIJ 1492 N LEU A 212 1 0 0 221 58 289 A N ATOM 1493 CA LEU A 21214.224 3.418 29.993 1.00 10.26 A C ANISOU 1493 CA LEU A 212 1398 11461150 −28 42 −5 A C SIGUIJ 1493 CA LEU A 212 1 0 0 220 74 290 A C ATOM1494 CB LEU A 212 15.269 2.772 30.919 1.00 11.19 A C ANISOU 1494 CB LEUA 212 1550 1227 1285 36 −83 −10 A C SIGUIJ 1494 CB LEU A 212 1 0 0 22074 290 A C ATOM 1495 CG LEU A 212 15.202 1.269 31.124 1.00 11.64 A CANISOU 1495 CG LEU A 212 2081 1226 1427 10 −103 −1 A C SIGUIJ 1495 CGLEU A 212 1 0 0 220 74 290 A C ATOM 1496 CD1 LEU A 212 16.503 0.80131.812 1.00 13.23 A C ANISOU 1496 CD1 LEU A 212 2352 1816 1871 325 −396−185 A C SIGUIJ 1496 CD1 LEU A 212 1 0 0 220 74 290 A C ATOM 1497 CD2LEU A 212 13.926 0.936 31.889 1.00 12.55 A C ANISOU 1497 CD2 LEU A 2122166 1628 1566 −103 −15 3 A C SIGUIJ 1497 CD2 LEU A 212 1 0 0 220 73 290A C ATOM 1498 C LEU A 212 14.578 4.861 29.800 1.00 9.76 A C ANISOU 1498C LEU A 212 1189 1144 1004 3 −1 0 A C SIGUIJ 1498 C LEU A 212 1 0 0 22073 290 A C ATOM 1499 O LEU A 212 15.520 5.197 29.089 1.00 9.43 A OANISOU 1499 O LEU A 212 1301 1173 1133 −33 127 −24 A O SIGUIJ 1499 O LEUA 212 1 0 0 221 52 289 A O ATOM 1500 N VAL A 213 13.833 5.751 30.4601.00 9.17 A N ANISOU 1500 N VAL A 213 1209 1140 1034 −9 27 −2 A N SIGUIJ1500 N VAL A 213 1 0 0 221 58 289 A N ATOM 1501 CA VAL A 213 14.1547.181 30.368 1.00 9.13 A C ANISOU 1501 CA VAL A 213 1190 1139 1156 −3 −10 A C SIGUIJ 1501 CA VAL A 213 1 0 0 220 73 290 A C ATOM 1502 CB VAL A213 13.218 8.032 31.250 1.00 9.23 A C ANISOU 1502 CB VAL A 213 1182 11411177 5 0 0 A C SIGUIJ 1502 CB VAL A 213 1 0 0 220 73 290 A C ATOM 1503CG1 VAL A 213 13.660 9.504 31.253 1.00 9.48 A C ANISOU 1503 CG1 VAL A213 1439 1156 1104 −66 −12 3 A C SIGUIJ 1503 CG1 VAL A 213 1 0 0 220 73290 A C ATOM 1504 CG2 VAL A 213 11.775 7.899 30.744 1.00 9.96 A C ANISOU1504 CG2 VAL A 213 1180 1430 1270 −20 −11 −2 A C SIGUIJ 1504 CG2 VAL A213 1 0 0 220 73 290 A C ATOM 1505 C VAL A 213 15.598 7.407 30.809 1.009.37 A C ANISOU 1505 C VAL A 213 1197 1166 1110 0 −1 0 A C SIGUIJ 1505 CVAL A 213 1 0 0 220 73 290 A C ATOM 1506 O VAL A 213 16.034 6.908 31.8531.00 9.26 A O ANISOU 1506 O VAL A 213 1222 1164 1104 2 5 0 A O SIGUIJ1506 O VAL A 213 1 0 0 221 52 289 A O ATOM 1507 N SER A 214 16.365 8.17930.025 1.00 9.91 A N ANISOU 1507 N SER A 214 1230 1174 1149 −6 6 −1 A NSIGUIJ 1507 N SER A 214 1 0 0 221 58 289 A N ATOM 1508 CA SER A 21417.741 8.499 30.404 1.00 10.45 A C ANISOU 1508 CA SER A 214 1243 12181162 −3 −2 0 A C SIGUIJ 1508 CA SER A 214 1 0 0 220 73 290 A C ATOM 1509CB SER A 214 18.721 7.915 29.375 1.00 10.69 A C ANISOU 1509 CB SER A 2141287 1334 1186 12 17 −1 A C SIGUIJ 1509 CB SER A 214 1 0 0 220 73 290 AC ATOM 1510 OG SER A 214 20.052 8.252 29.751 1.00 11.37 A O ANISOU 1510OG SER A 214 1317 1670 1351 −54 −5 −5 A O SIGUIJ 1510 OG SER A 214 1 0 0221 52 289 A O ATOM 1511 C SER A 214 17.939 9.995 30.598 1.00 10.93 A CANISOU 1511 C SER A 214 1507 1221 1162 −60 −4 1 A C SIGUIJ 1511 C SER A214 1 0 0 220 73 290 A C ATOM 1512 O SER A 214 18.233 10.427 31.739 1.0010.97 A O ANISOU 1512 O SER A 214 1600 1266 1166 −112 −10 3 A O SIGUIJ1512 O SER A 214 1 0 0 221 52 289 A O ATOM 1513 N TRP A 215 17.81810.827 29.547 1.00 11.11 A N ANISOU 1513 N TRP A 215 1267 1174 1161 −1315 −5 A N SIGUIJ 1513 N TRP A 215 1 0 0 221 58 289 A N ATOM 1514 CA TRP A215 18.158 12.208 29.728 1.00 11.48 A C ANISOU 1514 CA TRP A 215 14871186 1222 −193 9 −5 A C SIGUIJ 1514 CA TRP A 215 1 0 0 220 73 290 A CATOM 1515 CB TRP A 215 19.691 12.378 29.789 1.00 12.92 A C ANISOU 1515CB TRP A 215 1493 1681 1625 −256 6 7 A C SIGUIJ 1515 CB TRP A 215 1 0 0220 73 290 A C ATOM 1516 CG TRP A 215 20.366 12.319 28.523 1.00 14.50 AC ANISOU 1516 CG TRP A 215 1455 2674 1619 −221 −19 −18 A C SIGUIJ 1516CG TRP A 215 1 0 0 220 73 290 A C ATOM 1517 CD2 TRP A 215 20.791 13.45227.727 1.00 15.30 A C ANISOU 1517 CD2 TRP A 215 2034 2839 1760 −470 −6387 A C SIGUIJ 1517 CD2 TRP A 215 1 0 0 220 73 290 A C ATOM 1518 CE2 TRPA 215 21.384 12.931 26.581 1.00 15.68 A C ANISOU 1518 CE2 TRP A 215 22303125 1842 −414 6 −3 A C SIGUIJ 1518 CE2 TRP A 215 1 0 0 220 73 290 A CATOM 1519 CE3 TRP A 215 20.722 14.850 27.882 1.00 15.92 A C ANISOU 1519CE3 TRP A 215 2167 2842 2272 −470 14 20 A C SIGUIJ 1519 CE3 TRP A 215 10 0 220 73 290 A C ATOM 1520 CD1 TRP A 215 20.713 11.211 27.860 1.0014.56 A C ANISOU 1520 CD1 TRP A 215 1232 2691 1612 −237 −109 −47 A CSIGUIJ 1520 CD1 TRP A 215 1 0 0 220 73 290 A C ATOM 1521 NE1 TRP A 21521.347 11.562 26.668 1.00 15.70 A N ANISOU 1521 NE1 TRP A 215 1537 31291696 −395 8 9 A N SIGUIJ 1521 NE1 TRP A 215 1 0 0 221 58 289 A N ATOM1522 CZ2 TRP A 215 21.912 13.757 25.564 1.00 15.96 A C ANISOU 1522 CZ2TRP A 215 1958 3076 1872 −263 −12 33 A C SIGUIJ 1522 CZ2 TRP A 215 1 0 0220 73 290 A C ATOM 1523 CZ3 TRP A 215 21.252 15.664 26.885 1.00 16.39 AC ANISOU 1523 CZ3 TRP A 215 2166 2821 2253 −473 2 3 A C SIGUIJ 1523 CZ3TRP A 215 1 0 0 220 73 290 A C ATOM 1524 CH2 TRP A 215 21.836 15.10525.746 1.00 16.48 A C ANISOU 1524 CH2 TRP A 215 2473 3088 2274 −237 28−19 A C SIGUIJ 1524 CH2 TRP A 215 1 0 0 220 73 290 A C ATOM 1525 C TRP A215 17.590 13.041 28.594 1.00 11.26 A C ANISOU 1525 C TRP A 215 15921231 1237 −148 −17 6 A C SIGUIJ 1525 C TRP A 215 1 0 0 220 73 290 A CATOM 1526 O TRP A 215 17.105 12.544 27.569 1.00 11.36 A O ANISOU 1526 OTRP A 215 1550 1239 1220 −123 16 −6 A O SIGUIJ 1526 O TRP A 215 1 0 0221 52 289 A O ATOM 1527 N GLY A 216 17.666 14.362 28.758 1.00 11.41 A NANISOU 1527 N GLY A 216 1612 1223 1346 −140 −1 0 A N SIGUIJ 1527 N GLY A216 1 0 0 221 58 289 A N ATOM 1528 CA GLY A 216 17.274 15.281 27.6981.00 11.86 A C ANISOU 1528 CA GLY A 216 1773 1255 1381 −102 −43 10 A CSIGUIJ 1528 CA GLY A 216 1 0 0 220 73 290 A C ATOM 1529 C GLY A 21617.583 16.715 28.136 1.00 12.19 A C ANISOU 1529 C GLY A 216 1700 12631421 −100 −22 6 A C SIGUIJ 1529 C GLY A 216 1 0 0 220 73 290 A C ATOM1530 O GLY A 216 18.208 16.969 29.174 1.00 13.00 A O ANISOU 1530 O GLY A216 1985 1447 1491 −264 −143 64 A O SIGUIJ 1530 O GLY A 216 1 0 0 221 52289 A O ATOM 1531 N THR A 217 17.142 17.660 27.323 1.00 12.59 A N ANISOU1531 N THR A 217 1784 1270 1510 −152 −123 45 A N SIGUIJ 1531 N THR A 2171 0 0 221 58 289 A N ATOM 1532 CA THR A 217 17.446 19.081 27.539 1.0012.76 A C ANISOU 1532 CA THR A 217 1798 1290 1620 −179 34 −22 A C SIGUIJ1532 CA THR A 217 1 0 0 220 73 290 A C ATOM 1533 CB THR A 217 17.00619.861 26.284 1.00 13.20 A C ANISOU 1533 CB THR A 217 2318 1438 1753−248 −199 72 A C SIGUIJ 1533 CB THR A 217 1 0 0 220 72 290 A C ATOM 1534OG1 THR A 217 17.663 19.279 25.147 1.00 14.39 A O ANISOU 1534 OG1 THR A217 2455 1596 1805 −206 −136 36 A O SIGUIJ 1534 OG1 THR A 217 1 0 0 22152 289 A O ATOM 1535 CG2 THR A 217 17.284 21.349 26.393 1.00 14.24 A CANISOU 1535 CG2 THR A 217 3800 1489 2134 −517 −236 59 A C SIGUIJ 1535CG2 THR A 217 1 0 0 220 72 290 A C ATOM 1536 C THR A 217 16.691 19.62528.751 1.00 12.38 A C ANISOU 1536 C THR A 217 1688 1191 1556 −168 −40 30A C SIGUIJ 1536 C THR A 217 1 0 0 220 72 290 A C ATOM 1537 O THR A 21715.564 19.249 29.003 1.00 12.39 A O ANISOU 1537 O THR A 217 1713 13621514 −232 −45 35 A O SIGUIJ 1537 O THR A 217 1 0 0 221 52 289 A O ATOM1538 N PHE A 218 17.334 20.559 29.465 1.00 12.21 A N ANISOU 1538 N PHE A218 1757 1254 1572 −226 −28 20 A N SIGUIJ 1538 N PHE A 218 1 0 0 221 58289 A N ATOM 1539 CA PHE A 218 16.672 21.332 30.489 1.00 11.90 A CANISOU 1539 CA PHE A 218 1675 1246 1486 −208 −97 59 A C SIGUIJ 1539 CAPHE A 218 1 0 0 220 72 290 A C ATOM 1540 CB PHE A 218 17.356 21.05831.829 1.00 12.66 A C ANISOU 1540 CB PHE A 218 1933 1386 1551 −188 −22679 A C SIGUIJ 1540 CB PHE A 218 1 0 0 220 72 290 A C ATOM 1541 CG PHE A218 16.658 21.724 32.955 1.00 12.87 A C ANISOU 1541 CG PHE A 218 17301451 1439 −114 −385 103 A C SIGUIJ 1541 CG PHE A 218 1 0 0 220 72 290 AC ATOM 1542 CD1 PHE A 218 15.709 21.011 33.658 1.00 13.77 A C ANISOU1542 CD1 PHE A 218 2172 1757 1813 −381 −61 48 A C SIGUIJ 1542 CD1 PHE A218 1 0 0 220 72 290 A C ATOM 1543 CD2 PHE A 218 16.878 23.066 33.3111.00 13.74 A C ANISOU 1543 CD2 PHE A 218 1583 1452 1407 −86 −347 98 A CSIGUIJ 1543 CD2 PHE A 218 1 0 0 220 72 290 A C ATOM 1544 CE1 PHE A 21814.992 21.601 34.673 1.00 15.00 A C ANISOU 1544 CE1 PHE A 218 3044 22072268 −214 456 −105 A C SIGUIJ 1544 CE1 PHE A 218 1 0 0 220 72 290 A CATOM 1545 CE2 PHE A 218 16.144 23.611 34.327 1.00 13.52 A C ANISOU 1545CE2 PHE A 218 2007 1966 1633 86 −129 −59 A C SIGUIJ 1545 CE2 PHE A 218 10 0 220 72 290 A C ATOM 1546 CZ PHE A 218 15.221 22.887 34.986 1.0014.44 A C ANISOU 1546 CZ PHE A 218 2309 2150 2092 −19 167 −12 A C SIGUIJ1546 CZ PHE A 218 1 0 0 220 72 290 A C ATOM 1547 C PHE A 218 16.79922.832 30.114 1.00 11.95 A C ANISOU 1547 C PHE A 218 1447 1237 1419 −177−9 16 A C SIGUIJ 1547 C PHE A 218 1 0 0 220 72 290 A C ATOM 1548 O PHE A218 17.888 23.293 29.760 1.00 11.79 A O ANISOU 1548 O PHE A 218 14871509 1548 −289 −9 38 A O SIGUIJ 1548 O PHE A 218 1 0 0 221 52 289 A OATOM 1549 N PRO A 219 15.716 23.602 30.209 1.00 12.08 A N ANISOU 1549 NPRO A 219 1402 1167 1545 −231 −20 −31 A N SIGUIJ 1549 N PRO A 219 1 0 0221 58 289 A N ATOM 1550 CD PRO A 219 15.818 25.074 30.059 1.00 12.42 AC ANISOU 1550 CD PRO A 219 1998 1163 2680 −237 160 47 A C SIGUIJ 1550 CDPRO A 219 1 0 0 220 72 290 A C ATOM 1551 CA PRO A 219 14.375 23.20230.668 1.00 12.31 A C ANISOU 1551 CA PRO A 219 1418 1312 1570 −249 −1 −3A C SIGUIJ 1551 CA PRO A 219 1 0 0 220 72 290 A C ATOM 1552 CB PRO A 21913.572 24.525 30.678 1.00 12.41 A C ANISOU 1552 CB PRO A 219 1779 14491907 −23 8 1 A C SIGUIJ 1552 CB PRO A 219 1 0 0 220 72 290 A C ATOM 1553CG PRO A 219 14.642 25.560 30.920 1.00 12.69 A C ANISOU 1553 CG PRO A219 1875 1532 2386 −98 −87 1 A C SIGUIJ 1553 CG PRO A 219 1 0 0 220 72290 A C ATOM 1554 C PRO A 219 13.726 22.195 29.731 1.00 12.75 A C ANISOU1554 C PRO A 219 1553 1349 1561 −312 8 −21 A C SIGUIJ 1554 C PRO A 219 10 0 220 72 290 A C ATOM 1555 O PRO A 219 13.965 22.155 28.518 1.00 12.79A O ANISOU 1555 O PRO A 219 1686 1343 1555 −350 26 −33 A O SIGUIJ 1555 OPRO A 219 1 0 0 221 52 289 A O ATOM 1556 N CYS A 220 12.856 21.37230.336 1.00 12.93 A N ANISOU 1556 N CYS A 220 1508 1329 1644 −267 9 28 AN SIGUIJ 1556 N CYS A 220 1 0 0 221 58 289 A N ATOM 1557 CA CYS A 22012.062 20.357 29.618 1.00 13.60 A C ANISOU 1557 CA CYS A 220 1546 13221772 −246 −24 −18 A C SIGUIJ 1557 CA CYS A 220 1 0 0 220 72 290 A C ATOM1558 C CYS A 220 10.995 20.981 28.760 1.00 14.24 A C ANISOU 1558 C CYS A220 1693 1699 1739 0 −1 0 A C SIGUIJ 1558 C CYS A 220 1 0 0 220 72 290 AC ATOM 1559 O CYS A 220 10.615 22.141 28.942 1.00 14.47 A O ANISOU 1559O CYS A 220 1720 1704 1837 0 −8 0 A O SIGUIJ 1559 O CYS A 220 1 0 0 22152 289 A O ATOM 1560 CB CYS A 220 11.388 19.442 30.614 1.00 13.73 A CANISOU 1560 CB CYS A 220 1754 1357 1802 −333 3 −13 A C SIGUIJ 1560 CBCYS A 220 1 0 0 220 72 290 A C ATOM 1561 SG CYS A 220 12.591 18.60231.683 1.00 13.62 A S ANISOU 1561 SG CYS A 220 1825 1404 1757 −224 32−41 A S SIGUIJ 1561 SG CYS A 220 1 0 0 221 48 289 A S ATOM 1562 N GLY A220A 10.397 20.125 27.903 1.00 15.11 A N ANISOU 1562 N GLY A 220A 18381721 1732 −69 −4 2 A N SIGUIJ 1562 N GLY A 220A 1 0 0 221 58 289 A NATOM 1563 CA GLY A 220A 9.164 20.493 27.261 1.00 16.18 A C ANISOU 1563CA GLY A 220A 1866 2013 1719 38 10 0 A C SIGUIJ 1563 CA GLY A 220A 1 0 0220 72 290 A C ATOM 1564 C GLY A 220A 9.319 21.388 26.030 1.00 17.12 A CANISOU 1564 C GLY A 220A 2445 2220 1770 −339 −171 103 A C SIGUIJ 1564 CGLY A 220A 1 0 0 220 72 290 A C ATOM 1565 O GLY A 220A 8.307 21.86525.599 1.00 17.88 A O ANISOU 1565 O GLY A 220A 2713 2864 2256 17 −431−23 A O SIGUIJ 1565 O GLY A 220A 1 0 0 221 52 289 A O ATOM 1566 N GLN A221 10.490 21.594 25.449 1.00 18.02 A N ANISOU 1566 N GLN A 221 24971863 1947 −323 −72 36 A N SIGUIJ 1566 N GLN A 221 1 0 0 221 58 289 A NATOM 1567 CA GLN A 221 10.577 22.382 24.191 1.00 18.94 A C ANISOU 1567CA GLN A 221 2667 1946 1980 −453 −142 78 A C SIGUIJ 1567 CA GLN A 221 10 0 220 72 290 A C ATOM 1568 CB GLN A 221 12.033 22.912 23.978 1.0020.32 A C ANISOU 1568 CB GLN A 221 2735 2120 2808 −542 71 −128 A CSIGUIJ 1568 CB GLN A 221 1 0 0 220 72 290 A C ATOM 1569 CG GLN A 22112.698 23.650 25.232 1.00 22.63 A C ANISOU 1569 CG GLN A 221 6266 49612776 −3750 103 −97 A C SIGUIJ 1569 CG GLN A 221 1 0 0 220 71 290 A CATOM 1570 CD GLN A 221 14.309 23.668 25.301 1.00 23.50 A C ANISOU 1570CD GLN A 221 6269 5576 2798 −3749 109 −152 A C SIGUIJ 1570 CD GLN A 2211 0 0 220 71 290 A C ATOM 1571 OE1 GLN A 221 15.004 23.324 24.311 1.0024.98 A O ANISOU 1571 OE1 GLN A 221 6706 9542 2425 −1564 −346 0 A OSIGUIJ 1571 OE1 GLN A 221 1 0 0 221 52 289 A O ATOM 1572 NE2 GLN A 22114.893 24.082 26.507 1.00 24.32 A N ANISOU 1572 NE2 GLN A 221 4948 26022776 −1814 90 −60 A N SIGUIJ 1572 NE2 GLN A 221 1 0 0 221 58 289 A NATOM 1573 C GLN A 221 10.148 21.489 23.008 1.00 18.74 A C ANISOU 1573 CGLN A 221 2349 1846 1994 −295 −163 94 A C SIGUIJ 1573 C GLN A 221 1 0 0220 71 290 A C ATOM 1574 O GLN A 221 10.442 20.318 22.989 1.00 18.63 A OANISOU 1574 O GLN A 221 2832 1866 1658 −168 −431 60 A O SIGUIJ 1574 OGLN A 221 1 0 0 221 52 289 A O ATOM 1575 N PRO A 222 9.442 22.036 21.9941.00 18.66 A N ANISOU 1575 N PRO A 222 2444 2066 1903 −26 −84 5 A NSIGUIJ 1575 N PRO A 222 1 0 0 221 58 289 A N ATOM 1576 CD PRO A 2228.907 23.396 21.813 1.00 19.06 A C ANISOU 1576 CD PRO A 222 3241 21482479 226 −555 −114 A C SIGUIJ 1576 CD PRO A 222 1 0 0 220 71 290 A CATOM 1577 CA PRO A 222 9.126 21.153 20.865 1.00 18.29 A C ANISOU 1577 CAPRO A 222 2662 2088 1906 −76 −97 11 A C SIGUIJ 1577 CA PRO A 222 1 0 0220 71 290 A C ATOM 1578 CB PRO A 222 8.153 21.984 20.008 1.00 18.73 A CANISOU 1578 CB PRO A 222 3720 2824 2104 768 −489 −244 A C SIGUIJ 1578 CBPRO A 222 1 0 0 220 71 290 A C ATOM 1579 CG PRO A 222 8.573 23.37720.316 1.00 19.22 A C ANISOU 1579 CG PRO A 222 4653 2883 2550 569 −865−230 A C SIGUIJ 1579 CG PRO A 222 1 0 0 221 71 290 A C ATOM 1580 C PRO A222 10.348 20.770 20.082 1.00 18.03 A C ANISOU 1580 C PRO A 222 24121780 1354 −146 −451 81 A C SIGUIJ 1580 C PRO A 222 1 0 0 221 71 290 A CATOM 1581 O PRO A 222 11.340 21.500 20.052 1.00 17.67 A O ANISOU 1581 OPRO A 222 2510 1950 1890 −286 −507 188 A O SIGUIJ 1581 O PRO A 222 1 0 0221 52 289 A O ATOM 1582 N ASN A 223 10.273 19.628 19.426 1.00 17.53 A NANISOU 1582 N ASN A 223 2729 1793 1356 −225 −360 79 A N SIGUIJ 1582 NASN A 223 1 0 0 221 58 289 A N ATOM 1583 CA ASN A 223 11.350 19.14718.569 1.00 17.54 A C ANISOU 1583 CA ASN A 223 2780 1992 1428 −172 −32152 A C SIGUIJ 1583 CA ASN A 223 1 0 0 221 71 290 A C ATOM 1584 CB ASN A223 11.479 20.057 17.321 1.00 18.02 A C ANISOU 1584 CB ASN A 223 32491976 1422 −171 −278 33 A C SIGUIJ 1584 CB ASN A 223 1 0 0 221 71 290 A CATOM 1585 CG ASN A 223 10.215 20.035 16.501 1.00 18.59 A C ANISOU 1585CG ASN A 223 3261 2387 1455 −161 −297 34 A C SIGUIJ 1585 CG ASN A 223 10 0 221 71 290 A C ATOM 1586 OD1 ASN A 223 9.650 18.968 16.251 1.0018.98 A O ANISOU 1586 OD1 ASN A 223 3166 2340 1973 −58 −523 33 A OSIGUIJ 1586 OD1 ASN A 223 1 0 0 221 52 289 A O ATOM 1587 ND2 ASN A 2239.739 21.206 16.088 1.00 19.13 A N ANISOU 1587 ND2 ASN A 223 3123 23922721 −372 −737 299 A N SIGUIJ 1587 ND2 ASN A 223 1 0 0 221 58 289 A NATOM 1588 C ASN A 223 12.671 19.041 19.339 1.00 17.09 A C ANISOU 1588 CASN A 223 2793 1697 1502 −204 −358 59 A C SIGUIJ 1588 C ASN A 223 1 0 0221 71 290 A C ATOM 1589 O ASN A 223 13.738 19.351 18.853 1.00 17.57 A OANISOU 1589 O ASN A 223 2923 2765 1808 −476 −247 154 A O SIGUIJ 1589 OASN A 223 1 0 0 221 52 289 A O ATOM 1590 N ASP A 224 12.575 18.52120.560 1.00 16.25 A N ANISOU 1590 N ASP A 224 2538 1710 1506 −198 −36572 A N SIGUIJ 1590 N ASP A 224 1 0 0 221 58 289 A N ATOM 1591 CA ASP A224 13.720 18.394 21.449 1.00 15.80 A C ANISOU 1591 CA ASP A 224 24951541 1476 −242 −327 75 A C SIGUIJ 1591 CA ASP A 224 1 0 0 221 71 290 A CATOM 1592 CB ASP A 224 13.635 19.530 22.484 1.00 16.19 A C ANISOU 1592CB ASP A 224 2559 1555 1532 −384 −154 54 A C SIGUIJ 1592 CB ASP A 224 10 0 221 71 290 A C ATOM 1593 CG ASP A 224 14.929 19.735 23.242 1.0016.69 A C ANISOU 1593 CG ASP A 224 2561 1777 1561 −421 −159 67 A CSIGUIJ 1593 CG ASP A 224 1 0 0 221 71 290 A C ATOM 1594 OD1 ASP A 22415.907 19.005 22.994 1.00 17.24 A O ANISOU 1594 OD1 ASP A 224 2637 18662261 −364 −12 7 A O SIGUIJ 1594 OD1 ASP A 224 1 0 0 221 52 289 A O ATOM1595 OD2 ASP A 224 14.954 20.642 24.120 1.00 17.05 A O ANISOU 1595 OD2ASP A 224 2851 1892 1681 −652 75 −39 A O SIGUIJ 1595 OD2 ASP A 224 1 0 0221 52 289 A O ATOM 1596 C ASP A 224 13.581 17.040 22.170 1.00 14.99 A CANISOU 1596 C ASP A 224 1845 1478 1361 −19 −26 1 A C SIGUIJ 1596 C ASP A224 1 0 0 221 71 290 A C ATOM 1597 O ASP A 224 13.353 16.980 23.405 1.0015.33 A O ANISOU 1597 O ASP A 224 1951 1733 1369 −154 1 0 A O SIGUIJ1597 O ASP A 224 1 0 0 221 52 289 A O ATOM 1598 N PRO A 225 13.69815.928 21.441 1.00 14.29 A N ANISOU 1598 N PRO A 225 1966 1484 1360 −6754 −7 A N SIGUIJ 1598 N PRO A 225 1 0 0 221 58 289 A N ATOM 1599 CD PROA 225 14.105 15.840 20.019 1.00 14.25 A C ANISOU 1599 CD PRO A 225 26031703 1416 −202 249 −47 A C SIGUIJ 1599 CD PRO A 225 1 0 0 221 71 290 A CATOM 1600 CA PRO A 225 13.222 14.644 21.984 1.00 13.59 A C ANISOU 1600CA PRO A 225 1693 1481 1339 −15 −61 4 A C SIGUIJ 1600 CA PRO A 225 1 0 0221 71 290 A C ATOM 1601 CB PRO A 225 13.220 13.719 20.775 1.00 14.03 AC ANISOU 1601 CB PRO A 225 2427 1525 1340 −59 −27 2 A C SIGUIJ 1601 CBPRO A 225 1 0 0 221 71 290 A C ATOM 1602 CG PRO A 225 14.279 14.32319.833 1.00 14.43 A C ANISOU 1602 CG PRO A 225 2888 1702 1777 −198 407−66 A C SIGUIJ 1602 CG PRO A 225 1 0 0 221 71 290 A C ATOM 1603 C PRO A225 14.122 14.114 23.096 1.00 12.87 A C ANISOU 1603 C PRO A 225 15941510 1279 15 10 1 A C SIGUIJ 1603 C PRO A 225 1 0 0 221 71 290 A C ATOM1604 O PRO A 225 15.334 14.336 23.134 1.00 13.21 A O ANISOU 1604 O PRO A225 1601 1740 1530 −41 2 0 A O SIGUIJ 1604 O PRO A 225 1 0 0 221 52 289A O ATOM 1605 N GLY A 226 13.489 13.433 24.047 1.00 12.02 A N ANISOU1605 N GLY A 226 1575 1508 1262 −2 −16 0 A N SIGUIJ 1605 N GLY A 226 1 00 221 58 289 A N ATOM 1606 CA GLY A 226 14.217 12.778 25.138 1.00 11.76A C ANISOU 1606 CA GLY A 226 1492 1481 1217 0 44 0 A C SIGUIJ 1606 CAGLY A 226 1 0 0 221 71 290 A C ATOM 1607 C GLY A 226 14.917 11.52324.671 1.00 11.47 A C ANISOU 1607 C GLY A 226 1455 1465 1150 0 11 0 A CSIGUIJ 1607 C GLY A 226 1 0 0 221 71 290 A C ATOM 1608 O GLY A 22614.568 10.914 23.642 1.00 11.78 A O ANISOU 1608 O GLY A 226 1654 14871159 −69 11 −3 A O SIGUIJ 1608 O GLY A 226 1 0 0 221 52 289 A O ATOM1609 N VAL A 227 15.941 11.152 25.417 1.00 11.46 A N ANISOU 1609 N VAL A227 1406 1234 1142 −76 26 −9 A N SIGUIJ 1609 N VAL A 227 1 0 0 221 58289 A N ATOM 1610 CA VAL A 227 16.805 10.024 25.124 1.00 11.12 A CANISOU 1610 CA VAL A 227 1437 1245 1153 −46 20 −4 A C SIGUIJ 1610 CA VALA 227 1 0 0 221 71 290 A C ATOM 1611 CB VAL A 227 18.303 10.442 25.1801.00 11.78 A C ANISOU 1611 CB VAL A 227 1441 1335 1483 −72 0 0 A CSIGUIJ 1611 CB VAL A 227 1 0 0 221 71 290 A C ATOM 1612 CG1 VAL A 22719.175 9.313 24.627 1.00 12.98 A C ANISOU 1612 CG1 VAL A 227 1874 13802701 −54 678 −69 A C SIGUIJ 1612 CG1 VAL A 227 1 0 0 221 71 290 A C ATOM1613 CG2 VAL A 227 18.524 11.701 24.319 1.00 12.63 A C ANISOU 1613 CG2VAL A 227 2070 1541 1692 −417 −314 203 A C SIGUIJ 1613 CG2 VAL A 227 1 00 221 70 290 A C ATOM 1614 C VAL A 227 16.555 8.910 26.127 1.00 10.85 AC ANISOU 1614 C VAL A 227 1581 1223 1175 −4 111 −1 A C SIGUIJ 1614 C VALA 227 1 0 0 221 70 290 A C ATOM 1615 O VAL A 227 16.348 9.145 27.3411.00 10.23 A O ANISOU 1615 O VAL A 227 1443 1221 1168 −2 94 −1 A OSIGUIJ 1615 O VAL A 227 1 0 0 221 52 289 A O ATOM 1616 N TYR A 22816.566 7.703 25.586 1.00 10.02 A N ANISOU 1616 N TYR A 228 1415 12031169 4 91 2 A N SIGUIJ 1616 N TYR A 228 1 0 0 221 58 289 A N ATOM 1617CA TYR A 228 16.222 6.463 26.308 1.00 10.20 A C ANISOU 1617 CA TYR A 2281328 1217 1148 −22 6 −1 A C SIGUIJ 1617 CA TYR A 228 1 0 0 221 70 290 AC ATOM 1618 CB TYR A 228 14.913 5.863 25.811 1.00 9.96 A C ANISOU 1618CB TYR A 228 1316 1188 1210 10 −3 0 A C SIGUIJ 1618 CB TYR A 228 1 0 0221 70 290 A C ATOM 1619 CG TYR A 228 13.729 6.773 26.001 1.00 9.39 A CANISOU 1619 CG TYR A 228 1307 1182 1150 2 −3 0 A C SIGUIJ 1619 CG TYR A228 1 0 0 221 70 290 A C ATOM 1620 CD1 TYR A 228 13.533 7.897 25.1851.00 9.77 A C ANISOU 1620 CD1 TYR A 228 1420 1198 1189 −35 −68 10 A CSIGUIJ 1620 CD1 TYR A 228 1 0 0 221 70 290 A C ATOM 1621 CE1 TYR A 22812.492 8.749 25.388 1.00 10.19 A C ANISOU 1621 CE1 TYR A 228 1413 12061165 −44 −56 10 A C SIGUIJ 1621 CE1 TYR A 228 1 0 0 221 70 290 A C ATOM1622 CD2 TYR A 228 12.802 6.538 27.006 1.00 9.93 A C ANISOU 1622 CD2 TYRA 228 1315 1225 1146 −26 −7 1 A C SIGUIJ 1622 CD2 TYR A 228 1 0 0 221 70290 A C ATOM 1623 CE2 TYR A 228 11.746 7.360 27.192 1.00 10.22 A CANISOU 1623 CE2 TYR A 228 1341 1289 1105 4 −37 −2 A C SIGUIJ 1623 CE2TYR A 228 1 0 0 221 70 290 A C ATOM 1624 CZ TYR A 228 11.586 8.47126.404 1.00 10.10 A C ANISOU 1624 CZ TYR A 228 1391 1309 1156 −46 −73 23A C SIGUIJ 1624 CZ TYR A 228 1 0 0 221 70 290 A C ATOM 1625 OH TYR A 22810.478 9.265 26.651 1.00 11.60 A O ANISOU 1625 OH TYR A 228 1481 14161670 19 56 7 A O SIGUIJ 1625 OH TYR A 228 1 0 0 221 52 289 A O ATOM 1626C TYR A 228 17.290 5.436 26.099 1.00 10.30 A C ANISOU 1626 C TYR A 2281327 1224 1215 −20 8 −2 A C SIGUIJ 1626 C TYR A 228 1 0 0 221 70 290 A CATOM 1627 O TYR A 228 17.930 5.376 25.013 1.00 10.72 A O ANISOU 1627 OTYR A 228 1534 1590 1280 10 137 −24 A O SIGUIJ 1627 O TYR A 228 1 0 0221 52 289 A O ATOM 1628 N THR A 229 17.535 4.608 27.117 1.00 10.63 A NANISOU 1628 N THR A 229 1353 1217 1224 −11 7 −1 A N SIGUIJ 1628 N THR A229 1 0 0 221 58 289 A N ATOM 1629 CA THR A 229 18.329 3.402 26.944 1.0010.92 A C ANISOU 1629 CA THR A 229 1316 1211 1479 −30 37 −6 A C SIGUIJ1629 CA THR A 229 1 0 0 221 70 290 A C ATOM 1630 CB THR A 229 18.7532.865 28.305 1.00 11.62 A C ANISOU 1630 CB THR A 229 1564 1441 1509 1519 11 A C SIGUIJ 1630 CB THR A 229 1 0 0 221 70 290 A C ATOM 1631 OG1 THRA 229 19.487 3.872 28.948 1.00 12.39 A O ANISOU 1631 OG1 THR A 229 18101616 1576 −46 9 −2 A O SIGUIJ 1631 OG1 THR A 229 1 0 0 221 52 289 A OATOM 1632 CG2 THR A 229 19.679 1.680 28.226 1.00 12.39 A C ANISOU 1632CG2 THR A 229 1812 1563 1817 322 −11 −29 A C SIGUIJ 1632 CG2 THR A 229 10 0 221 70 290 A C ATOM 1633 C THR A 229 17.480 2.357 26.222 1.00 11.11A C ANISOU 1633 C THR A 229 1311 1182 1430 1 24 0 A C SIGUIJ 1633 C THRA 229 1 0 0 221 70 290 A C ATOM 1634 O THR A 229 16.345 2.041 26.6271.00 11.43 A O ANISOU 1634 O THR A 229 1374 1278 1621 −28 140 −30 A OSIGUIJ 1634 O THR A 229 1 0 0 221 52 289 A O ATOM 1635 N GLN A 23018.056 1.751 25.172 1.00 11.04 A N ANISOU 1635 N GLN A 230 1353 12141409 70 0 0 A N SIGUIJ 1635 N GLN A 230 1 0 0 221 58 289 A N ATOM 1636CA GLN A 230 17.336 0.791 24.322 1.00 11.88 A C ANISOU 1636 CA GLN A 2301491 1291 1412 −17 −8 1 A C SIGUIJ 1636 CA GLN A 230 1 0 0 221 70 290 AC ATOM 1637 CB GLN A 230 17.919 0.838 22.899 1.00 12.79 A C ANISOU 1637CB GLN A 230 1649 1657 1435 0 57 1 A C SIGUIJ 1637 CB GLN A 230 1 0 0221 70 290 A C ATOM 1638 CG GLN A 230 17.081 −0.002 21.922 1.00 13.79 AC ANISOU 1638 CG GLN A 230 1788 1661 1507 −12 −51 3 A C SIGUIJ 1638 CGGLN A 230 1 0 0 221 70 290 A C ATOM 1639 CD GLN A 230 17.584 0.00920.482 1.00 14.47 A C ANISOU 1639 CD GLN A 230 2306 2089 1555 59 122 20A C SIGUIJ 1639 CD GLN A 230 1 0 0 221 70 290 A C ATOM 1640 OE1 GLN A230 16.787 −0.260 19.527 1.00 16.05 A O ANISOU 1640 OE1 GLN A 230 27322441 1836 −9 −214 −4 A O SIGUIJ 1640 OE1 GLN A 230 1 0 0 221 52 289 A OATOM 1641 NE2 GLN A 230 18.860 0.287 20.314 1.00 14.61 A N ANISOU 1641NE2 GLN A 230 2271 1652 1107 167 76 13 A N SIGUIJ 1641 NE2 GLN A 230 1 00 221 58 289 A N ATOM 1642 C GLN A 230 17.450 −0.613 24.913 1.00 11.68 AC ANISOU 1642 C GLN A 230 1483 1291 1411 −9 −6 0 A C SIGUIJ 1642 C GLN A230 1 0 0 221 70 290 A C ATOM 1643 O GLN A 230 18.462 −1.287 24.762 1.0011.87 A O ANISOU 1643 O GLN A 230 1507 1344 1608 30 15 −2 A O SIGUIJ1643 O GLN A 230 1 0 0 221 52 289 A O ATOM 1644 N VAL A 231 16.404−1.043 25.609 1.00 11.59 A N ANISOU 1644 N VAL A 231 1481 1250 1408 3 −20 A N SIGUIJ 1644 N VAL A 231 1 0 0 221 58 289 A N ATOM 1645 CA VAL A231 16.447 −2.219 26.466 1.00 12.21 A C ANISOU 1645 CA VAL A 231 16121250 1440 34 29 4 A C SIGUIJ 1645 CA VAL A 231 1 0 0 221 70 290 A C ATOM1646 CB VAL A 231 15.087 −2.347 27.266 1.00 11.61 A C ANISOU 1646 CB VALA 231 1600 1317 1383 4 4 0 A C SIGUIJ 1646 CB VAL A 231 1 0 0 221 70 290A C ATOM 1647 CG1 VAL A 231 15.023 −3.633 28.014 1.00 12.29 A C ANISOU1647 CG1 VAL A 231 2296 1338 1493 129 294 41 A C SIGUIJ 1647 CG1 VAL A231 1 0 0 221 70 290 A C ATOM 1648 CG2 VAL A 231 14.982 −1.162 28.2571.00 12.18 A C ANISOU 1648 CG2 VAL A 231 1858 1317 1395 −39 79 −6 A CSIGUIJ 1648 CG2 VAL A 231 1 0 0 221 70 290 A C ATOM 1649 C VAL A 23116.754 −3.513 25.701 1.00 12.35 A C ANISOU 1649 C VAL A 231 1608 12471495 42 25 5 A C SIGUIJ 1649 C VAL A 231 1 0 0 221 70 290 A C ATOM 1650O VAL A 231 17.418 −4.398 26.242 1.00 12.73 A O ANISOU 1650 O VAL A 2311825 1361 1477 194 17 8 A O SIGUIJ 1650 O VAL A 231 1 0 0 221 52 289 A OATOM 1651 N CYS A 232 16.270 −3.612 24.464 1.00 13.22 A N ANISOU 1651 NCYS A 232 1737 1327 1550 76 −34 −9 A N SIGUIJ 1651 N CYS A 232 1 0 0 22158 289 A N ATOM 1652 CA CYS A 232 16.490 −4.834 23.661 1.00 14.33 A CANISOU 1652 CA CYS A 232 1699 1321 1642 57 −5 −3 A C SIGUIJ 1652 CA CYSA 232 1 0 0 221 70 290 A C ATOM 1653 C CYS A 232 17.967 −5.140 23.4081.00 14.77 A C ANISOU 1653 C CYS A 232 1706 1485 1870 99 2 0 A C SIGUIJ1653 C CYS A 232 1 0 0 221 69 290 A C ATOM 1654 O CYS A 232 18.307−6.249 22.935 1.00 15.41 A O ANISOU 1654 O CYS A 232 2325 1606 2081 356−158 −129 A O SIGUIJ 1654 O CYS A 232 1 0 0 221 52 289 A O ATOM 1655 CBCYS A 232 15.736 −4.752 22.312 1.00 14.90 A C ANISOU 1655 CB CYS A 2321979 1752 1751 299 −178 −142 A C SIGUIJ 1655 CB CYS A 232 1 0 0 221 69290 A C ATOM 1656 SG CYS A 232 16.414 −3.481 21.172 1.00 15.55 A SANISOU 1656 SG CYS A 232 2155 1860 1847 211 −149 −82 A S SIGUIJ 1656 SGCYS A 232 1 0 0 221 48 289 A S ATOM 1657 N LYS A 233 18.841 −4.18323.661 1.00 14.58 A N ANISOU 1657 N LYS A 233 1794 1605 1614 −18 55 −5 AN SIGUIJ 1657 N LYS A 233 1 0 0 221 58 289 A N ATOM 1658 CA LYS A 23320.281 −4.345 23.441 1.00 14.96 A C ANISOU 1658 CA LYS A 233 1793 19161589 20 34 −1 A C SIGUIJ 1658 CA LYS A 233 1 0 0 221 69 290 A C ATOM1659 CB LYS A 233 20.929 −3.013 23.048 1.00 15.39 A C ANISOU 1659 CB LYSA 233 1886 1930 1683 0 80 0 A C SIGUIJ 1659 CB LYS A 233 1 0 0 221 69290 A C ATOM 1660 CG LYS A 233 20.379 −2.387 21.745 1.00 15.68 A CANISOU 1660 CG LYS A 233 2041 1958 1709 1 15 0 A C SIGUIJ 1660 CG LYS A233 1 0 0 221 69 290 A C ATOM 1661 CD LYS A 233 20.467 −3.337 20.5171.00 16.47 A C ANISOU 1661 CD LYS A 233 2745 1994 1706 95 0 0 A C SIGUIJ1661 CD LYS A 233 1 0 0 221 69 290 A C ATOM 1662 CE LYS A 233 19.967−2.641 19.232 1.00 17.46 A C ANISOU 1662 CE LYS A 233 2704 2172 1689 22890 27 A C SIGUIJ 1662 CE LYS A 233 1 0 0 221 69 290 A C ATOM 1663 NZ LYSA 233 20.709 −1.429 18.892 1.00 18.10 A N ANISOU 1663 NZ LYS A 233 29102235 2165 148 274 53 A N SIGUIJ 1663 NZ LYS A 233 1 0 0 221 58 289 A NATOM 1664 C LYS A 233 20.980 −4.904 24.701 1.00 15.08 A C ANISOU 1664 CLYS A 233 1856 1893 1624 9 −11 1 A C SIGUIJ 1664 C LYS A 233 1 0 0 22169 290 A C ATOM 1665 O LYS A 233 22.189 −5.176 24.640 1.00 15.49 A OANISOU 1665 O LYS A 233 1892 2582 1999 169 14 −11 A O SIGUIJ 1665 O LYSA 233 1 0 0 221 52 289 A O ATOM 1666 N PHE A 234 20.240 −5.094 25.8001.00 15.18 A N ANISOU 1666 N PHE A 234 1817 1374 1619 144 −20 −10 A NSIGUIJ 1666 N PHE A 234 1 0 0 221 58 289 A N ATOM 1667 CA PHE A 23420.859 −5.419 27.104 1.00 15.35 A C ANISOU 1667 CA PHE A 234 2261 15371671 459 −178 −108 A C SIGUIJ 1667 CA PHE A 234 1 0 0 221 69 290 A CATOM 1668 CB PHE A 234 20.684 −4.191 28.069 1.00 14.40 A C ANISOU 1668CB PHE A 234 1588 1418 1521 216 19 26 A C SIGUIJ 1668 CB PHE A 234 1 0 0221 69 290 A C ATOM 1669 CG PHE A 234 21.476 −3.012 27.649 1.00 13.96 AC ANISOU 1669 CG PHE A 234 1811 1528 1422 48 24 3 A C SIGUIJ 1669 CG PHEA 234 1 0 0 221 69 290 A C ATOM 1670 CD1 PHE A 234 20.887 −1.978 26.9831.00 13.80 A C ANISOU 1670 CD1 PHE A 234 1831 1597 1406 126 113 40 A CSIGUIJ 1670 CD1 PHE A 234 1 0 0 221 69 290 A C ATOM 1671 CD2 PHE A 23422.840 −2.958 27.924 1.00 13.70 A C ANISOU 1671 CD2 PHE A 234 1813 19891645 32 −18 0 A C SIGUIJ 1671 CD2 PHE A 234 1 0 0 221 69 290 A C ATOM1672 CE1 PHE A 234 21.600 −0.882 26.570 1.00 13.55 A C ANISOU 1672 CE1PHE A 234 1929 1642 1311 38 87 8 A C SIGUIJ 1672 CE1 PHE A 234 1 0 0 22169 290 A C ATOM 1673 CE2 PHE A 234 23.558 −1.868 27.521 1.00 13.95 A CANISOU 1673 CE2 PHE A 234 1898 2016 1674 −10 6 0 A C SIGUIJ 1673 CE2 PHEA 234 1 0 0 221 69 290 A C ATOM 1674 CZ PHE A 234 22.926 −0.817 26.8321.00 13.72 A C ANISOU 1674 CZ PHE A 234 1939 2021 1667 5 6 0 A C SIGUIJ1674 CZ PHE A 234 1 0 0 221 69 290 A C ATOM 1675 C PHE A 234 20.267−6.695 27.739 1.00 16.19 A C ANISOU 1675 C PHE A 234 2047 1458 1584 530−224 −168 A C SIGUIJ 1675 C PHE A 234 1 0 0 221 69 290 A C ATOM 1676 OPHE A 234 20.407 −6.952 28.914 1.00 15.82 A O ANISOU 1676 O PHE A 2342292 1605 1585 596 −200 −134 A O SIGUIJ 1676 O PHE A 234 1 0 0 221 52289 A O ATOM 1677 N THR A 235 19.631 −7.513 26.902 1.00 17.36 A N ANISOU1677 N THR A 235 3328 1614 2113 297 −943 −160 A N SIGUIJ 1677 N THR A235 1 0 0 221 58 289 A N ATOM 1678 CA THR A 235 18.984 −8.754 27.3501.00 18.36 A C ANISOU 1678 CA THR A 235 3657 1659 2822 242 −637 −74 A CSIGUIJ 1678 CA THR A 235 1 0 0 221 69 290 A C ATOM 1679 CB THR A 23518.554 −9.620 26.125 1.00 19.04 A C ANISOU 1679 CB THR A 235 3239 17692587 −218 −159 27 A C SIGUIJ 1679 CB THR A 235 1 0 0 221 69 290 A C ATOM1680 OG1 THR A 235 17.678 −8.864 25.331 1.00 20.24 A O ANISOU 1680 OG1THR A 235 3786 2237 2696 253 −320 −59 A O SIGUIJ 1680 OG1 THR A 235 1 00 221 52 289 A O ATOM 1681 CG2 THR A 235 17.874 −10.902 26.570 1.0019.96 A C ANISOU 1681 CG2 THR A 235 4745 2126 2800 −925 101 −39 A CSIGUIJ 1681 CG2 THR A 235 1 0 0 221 69 290 A C ATOM 1682 C THR A 23519.912 −9.625 28.174 1.00 18.18 A C ANISOU 1682 C THR A 235 3252 16292358 211 −204 −35 A C SIGUIJ 1682 C THR A 235 1 0 0 221 69 290 A C ATOM1683 O THR A 235 19.536 −10.106 29.239 1.00 18.19 A O ANISOU 1683 O THRA 235 3132 1497 2331 257 −231 −64 A O SIGUIJ 1683 O THR A 235 1 0 0 22152 289 A O ATOM 1684 N LYS A 236 21.101 −9.821 27.631 1.00 18.29 A NANISOU 1684 N LYS A 236 3127 1760 1798 232 −481 −77 A N SIGUIJ 1684 NLYS A 236 1 0 0 221 58 289 A N ATOM 1685 CA LYS A 236 22.054 −10.72828.249 1.00 18.63 A C ANISOU 1685 CA LYS A 236 3363 2022 1616 529 −414−132 A C SIGUIJ 1685 CA LYS A 236 1 0 0 221 69 290 A C ATOM 1686 CB LYSA 236 23.253 −10.968 27.340 1.00 19.90 A C ANISOU 1686 CB LYS A 236 37422411 2145 727 32 14 A C SIGUIJ 1686 CB LYS A 236 1 0 0 221 69 290 A CATOM 1687 CG LYS A 236 24.209 −11.974 27.902 1.00 21.31 A C ANISOU 1687CG LYS A 236 4377 2728 2374 1155 −279 −150 A C SIGUIJ 1687 CG LYS A 2361 0 0 221 69 290 A C ATOM 1688 CD LYS A 236 25.310 −12.238 26.897 1.0022.84 A C ANISOU 1688 CD LYS A 236 6892 5054 4324 3275 1915 1570 A CSIGUIJ 1688 CD LYS A 236 1 0 0 221 69 290 A C ATOM 1689 CE LYS A 23626.216 −13.345 27.370 1.00 23.64 A C ANISOU 1689 CE LYS A 236 6392 30564572 1820 −527 −327 A C SIGUIJ 1689 CE LYS A 236 1 0 0 221 69 290 A CATOM 1690 NZ LYS A 236 27.456 −13.340 26.562 1.00 25.02 A N ANISOU 1690NZ LYS A 236 6797 13244 5535 2051 95 92 A N SIGUIJ 1690 NZ LYS A 236 1 00 221 58 289 A N ATOM 1691 C LYS A 236 22.526 −10.128 29.558 1.00 17.98A C ANISOU 1691 C LYS A 236 2715 1993 1706 1022 −413 −322 A C SIGUIJ1691 C LYS A 236 1 0 0 221 69 290 A C ATOM 1692 O LYS A 236 22.612−10.840 30.537 1.00 17.65 A O ANISOU 1692 O LYS A 236 3107 2053 17461159 −367 −267 A O SIGUIJ 1692 O LYS A 236 1 0 0 221 52 289 A O ATOM1693 N TRP A 237 22.889 −8.853 29.567 1.00 17.03 A N ANISOU 1693 N TRP A237 2618 1993 1781 1025 −409 −346 A N SIGUIJ 1693 N TRP A 237 1 0 0 22158 289 A N ATOM 1694 CA TRP A 237 23.384 −8.251 30.810 1.00 16.42 A CANISOU 1694 CA TRP A 237 2455 1988 1665 736 −256 −201 A C SIGUIJ 1694 CATRP A 237 1 0 0 221 69 290 A C ATOM 1695 CB TRP A 237 23.834 −6.81130.542 1.00 16.54 A C ANISOU 1695 CB TRP A 237 2900 2057 1693 573 −339−161 A C SIGUIJ 1695 CB TRP A 237 1 0 0 221 68 290 A C ATOM 1696 CG TRPA 237 24.301 −6.106 31.830 1.00 16.18 A C ANISOU 1696 CG TRP A 237 23082005 1448 199 72 23 A C SIGUIJ 1696 CG TRP A 237 1 0 0 221 68 290 A CATOM 1697 CD2 TRP A 237 23.479 −5.308 32.710 1.00 16.10 A C ANISOU 1697CD2 TRP A 237 2256 1884 1541 68 168 21 A C SIGUIJ 1697 CD2 TRP A 237 1 00 221 68 290 A C ATOM 1698 CE2 TRP A 237 24.264 −4.995 33.844 1.00 16.17A C ANISOU 1698 CE2 TRP A 237 2715 1863 1796 162 −178 −32 A C SIGUIJ1698 CE2 TRP A 237 1 0 0 221 68 290 A C ATOM 1699 CE3 TRP A 237 22.168−4.852 32.648 1.00 15.70 A C ANISOU 1699 CE3 TRP A 237 2222 1659 1712−13 160 −4 A C SIGUIJ 1699 CE3 TRP A 237 1 0 0 221 68 290 A C ATOM 1700CD1 TRP A 237 25.489 −6.214 32.420 1.00 16.78 A C ANISOU 1700 CD1 TRP A237 2436 2182 1896 260 −158 −85 A C SIGUIJ 1700 CD1 TRP A 237 1 0 0 22168 290 A C ATOM 1701 NE1 TRP A 237 25.485 −5.557 33.634 1.00 16.57 A NANISOU 1701 NE1 TRP A 237 2778 2169 1886 304 −182 −68 A N SIGUIJ 1701NE1 TRP A 237 1 0 0 221 58 289 A N ATOM 1702 CZ2 TRP A 237 23.766 −4.24734.944 1.00 15.98 A C ANISOU 1702 CZ2 TRP A 237 2724 1596 1905 −228 88−20 A C SIGUIJ 1702 CZ2 TRP A 237 1 0 0 221 68 290 A C ATOM 1703 CZ3 TRPA 237 21.680 −4.106 33.762 1.00 16.00 A C ANISOU 1703 CZ3 TRP A 237 23331699 1868 −218 354 −114 A C SIGUIJ 1703 CZ3 TRP A 237 1 0 0 221 68 290 AC ATOM 1704 CH2 TRP A 237 22.476 −3.832 34.861 1.00 16.05 A C ANISOU1704 CH2 TRP A 237 2714 1499 2033 −260 87 −25 A C SIGUIJ 1704 CH2 TRP A237 1 0 0 221 68 290 A C ATOM 1705 C TRP A 237 22.294 −8.322 31.896 1.0016.26 A C ANISOU 1705 C TRP A 237 2341 1815 1571 676 −369 −261 A CSIGUIJ 1705 C TRP A 237 1 0 0 221 68 290 A C ATOM 1706 O TRP A 23722.574 −8.590 33.053 1.00 15.65 A O ANISOU 1706 O TRP A 237 2261 18821557 952 −312 −302 A O SIGUIJ 1706 O TRP A 237 1 0 0 221 52 289 A O ATOM1707 N ILE A 238 21.056 −8.025 31.542 1.00 16.04 A N ANISOU 1707 N ILE A238 2313 1408 1693 542 −360 −201 A N SIGUIJ 1707 N ILE A 238 1 0 0 22158 289 A N ATOM 1708 CA ILE A 238 20.021 −8.050 32.574 1.00 16.27 A CANISOU 1708 CA ILE A 238 2361 1425 1756 531 −302 −181 A C SIGUIJ 1708 CAILE A 238 1 0 0 221 68 290 A C ATOM 1709 CB ILE A 238 18.660 −7.60631.953 1.00 15.62 A C ANISOU 1709 CB ILE A 238 2330 1440 1715 506 −265−149 A C SIGUIJ 1709 CB ILE A 238 1 0 0 221 68 290 A C ATOM 1710 CG2 ILEA 238 17.504 −7.904 32.910 1.00 15.95 A C ANISOU 1710 CG2 ILE A 238 25421960 2066 479 −14 −10 A C SIGUIJ 1710 CG2 ILE A 238 1 0 0 221 68 290 A CATOM 1711 CG1 ILE A 238 18.744 −6.118 31.573 1.00 15.59 A C ANISOU 1711CG1 ILE A 238 2375 1462 2087 558 −65 −65 A C SIGUIJ 1711 CG1 ILE A 238 10 0 221 68 290 A C ATOM 1712 CD1 ILE A 238 17.582 −5.630 30.631 1.0016.30 A C ANISOU 1712 CD1 ILE A 238 2398 1805 2074 675 −40 −45 A CSIGUIJ 1712 CD1 ILE A 238 1 0 0 221 68 290 A C ATOM 1713 C ILE A 23819.877 −9.455 33.193 1.00 16.58 A C ANISOU 1713 C ILE A 238 2917 14551938 494 −247 −97 A C SIGUIJ 1713 C ILE A 238 1 0 0 221 68 290 A C ATOM1714 O ILE A 238 19.856 −9.658 34.435 1.00 16.17 A O ANISOU 1714 O ILE A238 2618 1314 1932 523 −241 −124 A O SIGUIJ 1714 O ILE A 238 1 0 0 22152 289 A O ATOM 1715 N ASN A 239 19.772 −10.462 32.322 1.00 17.40 A NANISOU 1715 N ASN A 239 2720 1490 2022 587 −317 −168 A N SIGUIJ 1715 NASN A 239 1 0 0 221 58 289 A N ATOM 1716 CA ASN A 239 19.560 −11.82332.838 1.00 18.45 A C ANISOU 1716 CA ASN A 239 3345 1520 2166 463 −392−119 A C SIGUIJ 1716 CA ASN A 239 1 0 0 221 68 290 A C ATOM 1717 CB ASNA 239 19.189 −12.774 31.691 1.00 20.04 A C ANISOU 1717 CB ASN A 239 59801900 1951 −956 −63 15 A C SIGUIJ 1717 CB ASN A 239 1 0 0 221 68 290 A CATOM 1718 CG ASN A 239 17.805 −12.468 31.122 1.00 21.83 A C ANISOU 1718CG ASN A 239 6761 7810 5084 260 −1304 222 A C SIGUIJ 1718 CG ASN A 239 10 0 221 68 290 A C ATOM 1719 OD1 ASN A 239 16.900 −11.963 31.829 1.0023.50 A O ANISOU 1719 OD1 ASN A 239 7722 7660 7052 −1 110 −1 A O SIGUIJ1719 OD1 ASN A 239 1 0 0 221 52 289 A O ATOM 1720 ND2 ASN A 239 17.616−12.779 29.837 1.00 23.10 A N ANISOU 1720 ND2 ASN A 239 7909 9116 5160−83 −1388 −43 A N SIGUIJ 1720 ND2 ASN A 239 1 0 0 221 58 289 A N ATOM1721 C ASN A 239 20.751 −12.322 33.624 1.00 18.28 A C ANISOU 1721 C ASNA 239 3333 1689 2087 528 −329 −114 A C SIGUIJ 1721 C ASN A 239 1 0 0 22168 290 A C ATOM 1722 O ASN A 239 20.609 −12.859 34.727 1.00 18.24 A OANISOU 1722 O ASN A 239 3229 1606 2117 838 −192 −107 A O SIGUIJ 1722 OASN A 239 1 0 0 221 52 289 A O ATOM 1723 N ASP A 240 21.916 −12.03733.129 1.00 17.82 A N ANISOU 1723 N ASP A 240 3295 1342 1956 607 −371−137 A N SIGUIJ 1723 N ASP A 240 1 0 0 221 58 289 A N ATOM 1724 CA ASP A240 23.106 −12.575 33.751 1.00 18.10 A C ANISOU 1724 CA ASP A 240 37992334 2436 1243 −775 −496 A C SIGUIJ 1724 CA ASP A 240 1 0 0 221 68 290 AC ATOM 1725 CB ASP A 240 24.292 −12.406 32.852 1.00 19.02 A C ANISOU1725 CB ASP A 240 4137 1964 3126 1487 −286 −241 A C SIGUIJ 1725 CB ASP A240 1 0 0 221 68 290 A C ATOM 1726 CG ASP A 240 24.312 −13.411 31.7191.00 19.82 A C ANISOU 1726 CG ASP A 240 4105 1550 2819 841 274 121 A CSIGUIJ 1726 CG ASP A 240 1 0 0 221 68 290 A C ATOM 1727 OD1 ASP A 24023.383 −14.232 31.563 1.00 20.77 A O ANISOU 1727 OD1 ASP A 240 4301 18032990 618 284 87 A O SIGUIJ 1727 OD1 ASP A 240 1 0 0 221 52 289 A O ATOM1728 OD2 ASP A 240 25.296 −13.321 31.007 1.00 21.46 A O ANISOU 1728 OD2ASP A 240 4280 4063 3184 794 513 375 A O SIGUIJ 1728 OD2 ASP A 240 1 0 0221 52 289 A O ATOM 1729 C ASP A 240 23.423 −11.897 35.057 1.00 17.51 AC ANISOU 1729 C ASP A 240 2026 1656 1996 578 7 15 A C SIGUIJ 1729 C ASPA 240 1 0 0 221 68 290 A C ATOM 1730 O ASP A 240 23.894 −12.545 35.9961.00 17.50 A O ANISOU 1730 O ASP A 240 3155 1656 2025 974 −314 −198 A OSIGUIJ 1730 O ASP A 240 1 0 0 221 52 289 A O ATOM 1731 N THR A 24123.229 −10.574 35.130 1.00 16.51 A N ANISOU 1731 N THR A 241 1554 16422153 499 −25 18 A N SIGUIJ 1731 N THR A 241 1 0 0 221 58 289 A N ATOM1732 CA THR A 241 23.519 −9.853 36.374 1.00 15.98 A C ANISOU 1732 CA THRA 241 1904 1784 2151 226 6 −4 A C SIGUIJ 1732 CA THR A 241 1 0 0 221 68290 A C ATOM 1733 CB THR A 241 23.335 −8.344 36.168 1.00 15.61 A CANISOU 1733 CB THR A 241 2272 1779 1728 242 −129 −53 A C SIGUIJ 1733 CBTHR A 241 1 0 0 221 68 290 A C ATOM 1734 OG1 THR A 241 24.246 −7.92435.136 1.00 16.03 A O ANISOU 1734 OG1 THR A 241 2392 1887 1843 240 −16−7 A O SIGUIJ 1734 OG1 THR A 241 1 0 0 221 52 289 A O ATOM 1735 CG2 THRA 241 23.548 −7.565 37.496 1.00 15.96 A C ANISOU 1735 CG2 THR A 241 30061804 1768 311 −300 −72 A C SIGUIJ 1735 CG2 THR A 241 1 0 0 221 68 290 AC ATOM 1736 C THR A 241 22.581 −10.366 37.466 1.00 15.67 A C ANISOU 1736C THR A 241 1835 1394 2154 389 21 −17 A C SIGUIJ 1736 C THR A 241 1 0 0221 68 290 A C ATOM 1737 O THR A 241 22.981 −10.530 38.632 1.00 15.41 AO ANISOU 1737 O THR A 241 1953 1460 2163 397 −2 5 A O SIGUIJ 1737 O THRA 241 1 0 0 221 52 289 A O ATOM 1738 N MET A 242 21.309 −10.614 37.1531.00 15.65 A N ANISOU 1738 N MET A 242 1830 1169 2209 418 21 −13 A NSIGUIJ 1738 N MET A 242 1 0 0 221 58 289 A N ATOM 1739 CA MET A 24220.454 −11.169 38.182 1.00 16.26 A C ANISOU 1739 CA MET A 242 1834 13522191 308 −31 11 A C SIGUIJ 1739 CA MET A 242 1 0 0 221 68 290 A C ATOM1740 CB MET A 242 19.019 −11.306 37.688 1.00 16.02 A C ANISOU 1740 CBMET A 242 1872 1507 2567 294 −153 23 A C SIGUIJ 1740 CB MET A 242 1 0 0221 67 290 A C ATOM 1741 CG MET A 242 18.363 −9.924 37.474 1.00 15.38 AC ANISOU 1741 CG MET A 242 1839 1498 1717 289 −44 −48 A C SIGUIJ 1741 CGMET A 242 1 0 0 221 67 290 A C ATOM 1742 SD MET A 242 16.600 −9.97437.099 1.00 15.58 A S ANISOU 1742 SD MET A 242 1876 1638 2298 288 −182−86 A S SIGUIJ 1742 SD MET A 242 1 0 0 221 48 289 A S ATOM 1743 CE MET A242 16.608 −10.898 35.580 1.00 16.03 A C ANISOU 1743 CE MET A 242 22221519 2252 29 −1 0 A C SIGUIJ 1743 CE MET A 242 1 0 0 221 67 290 A C ATOM1744 C MET A 242 20.951 −12.552 38.622 1.00 17.07 A C ANISOU 1744 C META 242 2176 1393 2258 422 1 13 A C SIGUIJ 1744 C MET A 242 1 0 0 221 67290 A C ATOM 1745 O MET A 242 20.917 −12.839 39.831 1.00 17.17 A OANISOU 1745 O MET A 242 2211 1777 2277 403 5 81 A O SIGUIJ 1745 O MET A242 1 0 0 221 52 289 A O ATOM 1746 N LYS A 243 21.351 −13.402 37.6651.00 18.03 A N ANISOU 1746 N LYS A 243 2213 1425 2296 434 0 −21 A NSIGUIJ 1746 N LYS A 243 1 0 0 221 58 289 A N ATOM 1747 CA LYS A 24321.732 −14.770 38.034 1.00 19.06 A C ANISOU 1747 CA LYS A 243 2225 14242431 426 −3 6 A C SIGUIJ 1747 CA LYS A 243 1 0 0 221 67 290 A C ATOM1748 CB LYS A 243 21.848 −15.655 36.790 1.00 19.69 A C ANISOU 1748 CBLYS A 243 4005 1401 2430 522 65 17 A C SIGUIJ 1748 CB LYS A 243 1 0 0221 67 290 A C ATOM 1749 CG LYS A 243 20.535 −15.890 36.035 1.00 21.32 AC ANISOU 1749 CG LYS A 243 4461 3080 3739 308 −657 −170 A C SIGUIJ 1749CG LYS A 243 1 0 0 221 67 290 A C ATOM 1750 CD LYS A 243 20.933 −16.54334.700 1.00 22.30 A C ANISOU 1750 CD LYS A 243 10922 2563 4249 114 136421 A C SIGUIJ 1750 CD LYS A 243 1 0 0 221 67 290 A C ATOM 1751 CE LYS A243 19.867 −17.447 34.113 1.00 22.84 A C ANISOU 1751 CE LYS A 243 111892802 4638 −73 1171 −11 A C SIGUIJ 1751 CE LYS A 243 1 0 0 221 67 290 A CATOM 1752 NZ LYS A 243 19.720 −18.657 34.959 1.00 23.58 A N ANISOU 1752NZ LYS A 243 3968 2803 4447 8 32 0 A N SIGUIJ 1752 NZ LYS A 243 1 0 0221 58 289 A N ATOM 1753 C LYS A 243 23.036 −14.780 38.811 1.00 19.41 AC ANISOU 1753 C LYS A 243 2221 1771 2421 444 2 −6 A C SIGUIJ 1753 C LYSA 243 1 0 0 221 67 290 A C ATOM 1754 O LYS A 243 23.251 −15.704 39.6311.00 19.49 A O ANISOU 1754 O LYS A 243 2813 1899 2495 659 77 85 A OSIGUIJ 1754 O LYS A 243 1 0 0 221 52 289 A O ATOM 1755 N LYS A 24423.897 −13.795 38.577 1.00 19.53 A N ANISOU 1755 N LYS A 244 2133 16882068 511 −36 −68 A N SIGUIJ 1755 N LYS A 244 1 0 0 221 58 289 A N ATOM1756 CA LYS A 244 25.157 −13.728 39.293 1.00 20.25 A C ANISOU 1756 CALYS A 244 2154 1775 2169 541 −75 −148 A C SIGUIJ 1756 CA LYS A 244 1 0 0221 67 290 A C ATOM 1757 CB LYS A 244 26.178 −12.970 38.454 1.00 20.71 AC ANISOU 1757 CB LYS A 244 2628 2639 2411 −3 4 1 A C SIGUIJ 1757 CB LYSA 244 1 0 0 221 67 290 A C ATOM 1758 CG LYS A 244 26.607 −13.844 37.2661.00 21.33 A C ANISOU 1758 CG LYS A 244 2939 2704 2415 146 5 2 A CSIGUIJ 1758 CG LYS A 244 1 0 0 221 67 290 A C ATOM 1759 CD LYS A 24427.426 −13.149 36.237 1.00 22.40 A C ANISOU 1759 CD LYS A 244 3516 30052578 −172 256 −61 A C SIGUIJ 1759 CD LYS A 244 1 0 0 221 67 290 A C ATOM1760 CE LYS A 244 27.046 −13.689 34.891 1.00 23.00 A C ANISOU 1760 CELYS A 244 5164 2662 2883 853 −627 −206 A C SIGUIJ 1760 CE LYS A 244 1 00 221 67 290 A C ATOM 1761 NZ LYS A 244 28.051 −13.198 33.885 1.00 23.58A N ANISOU 1761 NZ LYS A 244 6818 5829 3878 −592 322 −106 A N SIGUIJ1761 NZ LYS A 244 1 0 0 221 58 289 A N ATOM 1762 C LYS A 244 25.059−13.148 40.701 1.00 20.44 A C ANISOU 1762 C LYS A 244 2240 1405 2114 427−7 −9 A C SIGUIJ 1762 C LYS A 244 1 0 0 221 67 290 A C ATOM 1763 O LYS A244 26.033 −13.177 41.458 1.00 20.15 A O ANISOU 1763 O LYS A 244 22612172 2151 487 −32 −52 A O SIGUIJ 1763 O LYS A 244 1 0 0 221 51 289 A OATOM 1764 N HIS A 245 23.893 −12.629 41.059 1.00 21.08 A N ANISOU 1764 NHIS A 245 2292 1885 1853 610 −111 −105 A N SIGUIJ 1764 N HIS A 245 1 0 0221 57 289 A N ATOM 1765 CA HIS A 245 23.699 −12.026 42.375 1.00 22.18 AC ANISOU 1765 CA HIS A 245 2118 1610 1826 331 −11 −8 A C SIGUIJ 1765 CAHIS A 245 1 0 0 221 67 290 A C ATOM 1766 CB HIS A 245 23.528 −10.49842.280 1.00 21.47 A C ANISOU 1766 CB HIS A 245 2113 1618 2489 343 −60 21A C SIGUIJ 1766 CB HIS A 245 1 0 0 221 67 290 A C ATOM 1767 CG HIS A 24524.756 −9.806 41.809 1.00 21.54 A C ANISOU 1767 CG HIS A 245 2208 16832698 274 39 −9 A C SIGUIJ 1767 CG HIS A 245 1 0 0 221 67 290 A C ATOM1768 CD2 HIS A 245 25.094 −9.348 40.592 1.00 21.75 A C ANISOU 1768 CD2HIS A 245 2595 1985 2703 −38 20 11 A C SIGUIJ 1768 CD2 HIS A 245 1 0 0221 67 290 A C ATOM 1769 ND1 HIS A 245 25.856 −9.605 42.618 1.00 22.01 AN ANISOU 1769 ND1 HIS A 245 2583 3631 3237 −101 −356 −39 A N SIGUIJ 1769ND1 HIS A 245 1 0 0 221 57 289 A N ATOM 1770 CE1 HIS A 245 26.818 −9.04741.910 1.00 21.93 A C ANISOU 1770 CE1 HIS A 245 2767 3493 3671 0 −48 0 AC SIGUIJ 1770 CE1 HIS A 245 1 0 0 221 67 290 A C ATOM 1771 NE2 HIS A 24526.379 −8.876 40.682 1.00 21.98 A N ANISOU 1771 NE2 HIS A 245 2697 26723671 −298 −44 5 A N SIGUIJ 1771 NE2 HIS A 245 1 0 0 221 57 289 A N ATOM1772 C HIS A 245 22.478 −12.610 43.050 1.00 23.41 A C ANISOU 1772 C HISA 245 2277 2229 1876 16 4 1 A C SIGUIJ 1772 C HIS A 245 1 0 0 221 67 290A C ATOM 1773 O HIS A 245 21.673 −11.862 43.634 1.00 23.57 A O ANISOU1773 O HIS A 245 3593 2566 2676 683 1018 474 A O SIGUIJ 1773 O HIS A 2451 0 0 221 51 289 A O ATOM 1774 N ARG A 246 22.331 −13.935 43.000 1.0024.99 A N ANISOU 1774 N ARG A 246 2645 2244 3081 −2 −411 11 A N SIGUIJ1774 N ARG A 246 1 0 0 221 57 289 A N ATOM 1775 CA ARG A 246 21.272−14.563 43.756 1.00 26.54 A C ANISOU 1775 CA ARG A 246 3755 2997 5101−286 913 201 A C SIGUIJ 1775 CA ARG A 246 1 0 0 221 67 290 A C ATOM 1776CB ARG A 246 21.219 −16.057 43.462 1.00 27.41 A C ANISOU 1776 CB ARG A246 3507 3031 6293 −54 −129 9 A C SIGUIJ 1776 CB ARG A 246 1 0 0 221 67290 A C ATOM 1777 CG ARG A 246 21.319 −16.302 42.001 1.00 28.73 A CANISOU 1777 CG ARG A 246 8214 3342 6310 616 83 8 A C SIGUIJ 1777 CG ARGA 246 1 0 0 221 67 290 A C ATOM 1778 CD ARG A 246 20.574 −17.528 41.5981.00 29.81 A C ANISOU 1778 CD ARG A 246 15256 5457 7745 −3138 −1525 513A C SIGUIJ 1778 CD ARG A 246 1 0 0 221 67 290 A C ATOM 1779 NE ARG A 24619.632 −17.212 40.533 1.00 30.72 A N ANISOU 1779 NE ARG A 246 13748 87305920 −1374 343 −74 A N SIGUIJ 1779 NE ARG A 246 1 0 0 221 57 289 A NATOM 1780 CZ ARG A 246 18.420 −17.731 40.467 1.00 31.19 A C ANISOU 1780CZ ARG A 246 13449 7175 6111 −710 314 −33 A C SIGUIJ 1780 CZ ARG A 246 10 0 221 67 290 A C ATOM 1781 NH1 ARG A 246 18.022 −18.576 41.414 1.0031.95 A N ANISOU 1781 NH1 ARG A 246 8876 6548 5694 477 −548 −94 A NSIGUIJ 1781 NH1 ARG A 246 1 0 0 221 57 289 A N ATOM 1782 NH2 ARG A 24617.641 −17.451 39.445 1.00 31.97 A N ANISOU 1782 NH2 ARG A 246 1384410033 6150 253 282 14 A N SIGUIJ 1782 NH2 ARG A 246 1 0 0 221 57 289 A NATOM 1783 C ARG A 246 21.456 −14.309 45.240 1.00 26.93 A C ANISOU 1783 CARG A 246 11079 4350 5249 −654 62 −6 A C SIGUIJ 1783 C ARG A 246 1 0 0221 67 290 A C ATOM 1784 O ARG A 246 20.426 −13.976 45.883 1.00 27.58 AO ANISOU 1784 O ARG A 246 11357 3254 6365 −1074 717 −122 A O SIGUIJ 1784O ARG A 246 1 0 0 221 51 289 A O ATOM 1785 OXT ARG A 246 22.610 −14.43045.737 1.00 27.58 A O ANISOU 1785 OXT ARG A 246 10736 6341 3324 −426 899−68 A O SIGUIJ 1785 OXT ARG A 246 1 0 0 221 51 289 A O TER 1 ARG A 246 AHETATM 1786 OH2 WAT S  1 24.781 −18.805 43.324 1.00 6.43 S O ANISOU 1786OH2 WAT S  1 1173 478 1393 453 −95 153 S O SIGUIJ 1786 OH2 WAT S  1 1 00 221 51 289 S O HETATM 1787 OH2 WAT S  2 4.474 5.063 48.501 1.00 9.59 SO ANISOU 1787 OH2 WAT S  2 1494 1440 1186 −3 68 −4 S O SIGUIJ 1787 OH2WAT S  2 1 0 0 221 51 289 S O HETATM 1788 OH2 WAT S  3 15.552 4.96551.375 1.00 9.82 S O ANISOU 1788 OH2 WAT S  3 1326 1720 965 −369 −36 47S O SIGUIJ 1788 OH2 WAT S  3 1 0 0 221 51 289 S O HETATM 1789 OH2 WAT S 4 8.858 8.363 37.689 1.00 10.14 S O ANISOU 1789 OH2 WAT S  4 1162 11901480 −1 −18 0 S O SIGUIJ 1789 OH2 WAT S  4 1 0 0 221 51 289 S O HETATM1790 OH2 WAT S  5 4.835 12.969 35.509 1.00 9.64 S O ANISOU 1790 OH2 WATS  5 1150 1216 1326 6 10 −1 S O SIGUIJ 1790 OH2 WAT S  5 1 0 0 221 51289 S O HETATM 1791 OH2 WAT S  6 9.341 7.161 35.215 1.00 10.61 S OANISOU 1791 OH2 WAT S  6 1360 1161 1548 172 −2 1 S O SIGUIJ 1791 OH2 WATS  6 1 0 0 221 51 289 S O HETATM 1792 OH2 WAT S  7 21.178 9.235 41.8111.00 10.42 S O ANISOU 1792 OH2 WAT S  7 1321 1163 1465 −114 0 0 S OSIGUIJ 1792 OH2 WAT S  7 1 0 0 221 51 289 S O HETATM 1793 OH2 WAT S  827.008 −0.037 40.833 1.00 10.86 S O ANISOU 1793 OH2 WAT S  8 1231 15461387 −17 −262 −13 S O SIGUIJ 1793 OH2 WAT S  8 1 0 0 221 51 289 S OHETATM 1794 OH2 WAT S  9 5.785 12.849 42.062 1.00 12.65 S O ANISOU 1794OH2 WAT S  9 1871 1478 1529 256 11 6 S O SIGUIJ 1794 OH2 WAT S  9 1 0 0221 51 289 S O HETATM 1795 OH2 WAT S  10 25.809 10.089 36.957 1.00 15.33S O ANISOU 1795 OH2 WAT S  10 1699 2881 1728 75 −357 −1336 S O SIGUIJ1795 OH2 WAT S  10 1 0 0 221 51 289 S O HETATM 1796 OH2 WAT S  11 2.66619.022 31.476 1.00 12.71 S O ANISOU 1796 OH2 WAT S  11 2071 1417 1720363 −179 −112 S O SIGUIJ 1796 OH2 WAT S  11 1 0 0 221 51 289 S O HETATM1797 OH2 WAT S  12 4.947 3.340 30.044 1.00 15.53 S O ANISOU 1797 OH2 WATS  12 2033 1941 1721 −379 55 −55 S O SIGUIJ 1797 OH2 WAT S  12 1 0 0 22151 289 S O HETATM 1798 OH2 WAT S  13 13.902 −0.433 19.971 1.00 15.89 S OANISOU 1798 OH2 WAT S  13 2696 1999 1557 −396 −358 132 S O SIGUIJ 1798OH2 WAT S  13 1 0 0 221 51 289 S O HETATM 1799 OH2 WAT S  14 21.9004.419 27.895 1.00 14.56 S O ANISOU 1799 OH2 WAT S  14 1917 1895 1557 −4318 −35 S O SIGUIJ 1799 OH2 WAT S  14 1 0 0 221 51 289 S O HETATM 1800OH2 WAT S  15 4.033 −1.934 40.854 1.00 13.63 S O ANISOU 1800 OH2 WAT S 15 2107 1352 1711 −295 383 −146 S O SIGUIJ 1800 OH2 WAT S  15 1 0 0 22151 289 S O HETATM 1801 OH2 WAT S  16 22.787 8.096 47.811 1.00 13.85 S OANISOU 1801 OH2 WAT S  16 2167 1748 1779 −701 88 −98 S O SIGUIJ 1801 OH2WAT S  16 1 0 0 221 51 289 S O HETATM 1802 OH2 WAT S  17 19.119 8.94733.793 1.00 11.52 S O ANISOU 1802 OH2 WAT S  17 1384 1642 1345 116 0 −1S O SIGUIJ 1802 OH2 WAT S  17 1 0 0 221 51 289 S O HETATM 1803 OH2 WAT S 18 19.344 12.504 33.386 1.00 16.02 S O ANISOU 1803 OH2 WAT S  18 19162583 1861 −430 −3 −19 S O SIGUIJ 1803 OH2 WAT S  18 1 0 0 221 51 289 S OHETATM 1804 OH2 WAT S  19 −0.352 11.477 24.455 1.00 18.54 S O ANISOU1804 OH2 WAT S  19 1767 2696 2887 698 −42 24 S O SIGUIJ 1804 OH2 WAT S 19 1 0 0 221 51 289 S O HETATM 1805 OH2 WAT S  20 2.073 15.464 31.9011.00 14.28 S O ANISOU 1805 OH2 WAT S  20 1612 1934 1675 73 0 0 S OSIGUIJ 1805 OH2 WAT S  20 1 0 0 221 51 289 S O HETATM 1806 OH2 WAT S  211.417 20.832 35.391 1.00 14.41 S O ANISOU 1806 OH2 WAT S  21 1725 13501965 347 49 −56 S O SIGUIJ 1806 OH2 WAT S  21 1 0 0 221 51 289 S OHETATM 1807 OH2 WAT S  22 0.109 −4.786 46.294 1.00 24.10 S O ANISOU 1807OH2 WAT S  22 3431 2852 2764 1027 639 544 S O SIGUIJ 1807 OH2 WAT S  221 0 0 221 51 289 S O HETATM 1808 OH2 WAT S  23 5.790 −5.960 50.260 1.0019.83 S O ANISOU 1808 OH2 WAT S  23 2406 2846 1833 −107 −54 −1 S OSIGUIJ 1808 OH2 WAT S  23 1 0 0 221 51 289 S O HETATM 1809 OH2 WAT S  2425.312 −2.553 46.116 1.00 18.04 S O ANISOU 1809 OH2 WAT S  24 1597 33262535 −196 −79 −12 S O SIGUIJ 1809 OH2 WAT S  24 1 0 0 221 51 289 S OHETATM 1810 OH2 WAT S  25 22.872 0.557 46.323 1.00 14.62 S O ANISOU 1810OH2 WAT S  25 2126 1823 1778 50 −471 −49 S O SIGUIJ 1810 OH2 WAT S  25 10 0 221 51 289 S O HETATM 1811 OH2 WAT S  26 14.410 −1.902 23.124 1.0014.14 S O ANISOU 1811 OH2 WAT S  26 1804 1976 1647 34 12 0 S O SIGUIJ1811 OH2 WAT S  26 1 0 0 221 51 289 S O HETATM 1812 OH2 WAT S  27 13.75518.203 27.222 1.00 15.46 S O ANISOU 1812 OH2 WAT S  27 2007 1739 1669−309 −51 39 S O SIGUIJ 1812 OH2 WAT S  27 1 0 0 221 51 289 S O HETATM1813 OH2 WAT S  28 10.386 11.514 25.133 1.00 13.16 S O ANISOU 1813 OH2WAT S  28 1921 1495 1499 105 −40 −9 S O SIGUIJ 1813 OH2 WAT S  28 1 0 0221 51 289 S O HETATM 1814 OH2 WAT S  29 6.031 24.167 32.208 1.00 17.37S O ANISOU 1814 OH2 WAT S  29 2381 1712 2309 131 7 7 S O SIGUIJ 1814 OH2WAT S  29 1 0 0 221 51 289 S O HETATM 1815 OH2 WAT S  30 15.062 16.50025.595 1.00 15.15 S O ANISOU 1815 OH2 WAT S  30 2188 1659 1772 −298 −402181 S O SIGUIJ 1815 OH2 WAT S  30 1 0 0 221 51 289 S O HETATM 1816 OH2WAT S  31 10.624 25.090 41.301 1.00 21.60 S O ANISOU 1816 OH2 WAT S  312700 2652 3111 2 −47 −1 S O SIGUIJ 1816 OH2 WAT S  31 1 0 0 221 51 289 SO HETATM 1817 OH2 WAT S  32 2.808 3.760 50.728 1.00 21.37 S O ANISOU1817 OH2 WAT S  32 2182 4019 2257 191 2 −2 S O SIGUIJ 1817 OH2 WAT S  321 0 0 221 51 289 S O HETATM 1818 OH2 WAT S  33 16.530 15.962 17.042 1.0018.16 S O ANISOU 1818 OH2 WAT S  33 2819 2566 2015 −16 365 1 S O SIGUIJ1818 OH2 WAT S  33 1 0 0 221 51 289 S O HETATM 1819 OH2 WAT S  34 5.585−3.559 51.423 1.00 18.93 S O ANISOU 1819 OH2 WAT S  34 2586 3629 1722−468 25 −3 S O SIGUIJ 1819 OH2 WAT S  34 1 0 0 221 51 289 S O HETATM1820 OH2 WAT S  35 21.770 19.513 27.539 1.00 29.03 S O ANISOU 1820 OH2WAT S  35 3155 4624 3657 −761 −2 −1 S O SIGUIJ 1820 OH2 WAT S  35 1 0 0221 51 289 S O HETATM 1821 OH2 WAT S  36 13.143 20.680 26.241 1.00 16.62S O ANISOU 1821 OH2 WAT S  36 1927 2059 1723 −15 −4 0 S O SIGUIJ 1821OH2 WAT S  36 1 0 0 221 51 289 S O HETATM 1822 OH2 WAT S  37 −1.1060.388 37.477 1.00 17.68 S O ANISOU 1822 OH2 WAT S  37 1816 1896 2547 −6132 5 S O SIGUIJ 1822 OH2 WAT S  37 1 0 0 221 51 289 S O HETATM 1823 OH2WAT S  38 11.350 17.436 28.280 1.00 16.01 S O ANISOU 1823 OH2 WAT S  382491 1513 1556 −353 −439 141 S O SIGUIJ 1823 OH2 WAT S  38 1 0 0 221 51289 S O HETATM 1824 OH2 WAT S  39 23.589 −7.362 27.067 1.00 19.07 S OANISOU 1824 OH2 WAT S  39 2961 2213 2026 1059 −110 −97 S O SIGUIJ 1824OH2 WAT S  39 1 0 0 221 51 289 S O HETATM 1825 OH2 WAT S  40 19.429−5.617 48.324 1.00 17.18 S O ANISOU 1825 OH2 WAT S  40 1922 2364 1913272 −3 9 S O SIGUIJ 1825 OH2 WAT S  40 1 0 0 221 51 289 S O HETATM 1826OH2 WAT S  41 9.243 16.808 19.409 1.00 17.74 S O ANISOU 1826 OH2 WAT S 41 2768 1982 2206 −321 −314 128 S O SIGUIJ 1826 OH2 WAT S  41 1 0 0 22151 289 S O HETATM 1827 OH2 WAT S  42 8.159 −7.341 50.894 1.00 19.75 S OANISOU 1827 OH2 WAT S  42 2982 2433 2025 −328 −349 137 S O SIGUIJ 1827OH2 WAT S  42 1 0 0 221 51 289 S O HETATM 1828 OH2 WAT S  43 24.526−15.892 42.152 1.00 19.49 S O ANISOU 1828 OH2 WAT S  43 3887 1662 2311514 −288 −76 S O SIGUIJ 1828 OH2 WAT S  43 1 0 0 221 51 289 S O HETATM1829 OH2 WAT S  44 15.071 0.754 16.873 1.00 23.52 S O ANISOU 1829 OH2WAT S  44 2962 3462 2125 −799 −23 14 S O SIGUIJ 1829 OH2 WAT S  44 1 0 0221 51 289 S O HETATM 1830 OH2 WAT S  45 1.623 1.863 38.928 1.00 19.00 SO ANISOU 1830 OH2 WAT S  45 2163 2827 2281 252 −5 5 S O SIGUIJ 1830 OH2WAT S  45 1 0 0 221 51 289 S O HETATM 1831 OH2 WAT S  46 1.083 11.64021.244 1.00 20.42 S O ANISOU 1831 OH2 WAT S  46 2274 2112 2993 9 −227 −8S O SIGUIJ 1831 OH2 WAT S  46 1 0 0 221 51 289 S O HETATM 1832 OH2 WAT S 47 −0.976 −2.337 46.128 1.00 20.63 S O ANISOU 1832 OH2 WAT S  47 30911922 2501 −91 62 −7 S O SIGUIJ 1832 OH2 WAT S  47 1 0 0 221 51 289 S OHETATM 1833 OH2 WAT S  48 −1.532 3.190 35.408 1.00 18.27 S O ANISOU 1833OH2 WAT S  48 2523 2040 2240 155 13 5 S O SIGUIJ 1833 OH2 WAT S  48 1 00 221 51 289 S O HETATM 1834 OH2 WAT S  49 10.268 17.052 21.922 1.0015.72 S O ANISOU 1834 OH2 WAT S  49 2308 2056 1739 −85 −374 70 S OSIGUIJ 1834 OH2 WAT S  49 1 0 0 221 51 289 S O HETATM 1835 OH2 WAT S  5013.003 −12.816 35.683 1.00 20.60 S O ANISOU 1835 OH2 WAT S  50 3574 20192471 410 −281 −85 S O SIGUIJ 1835 OH2 WAT S  50 1 0 0 221 51 289 S OHETATM 1836 OH2 WAT S  51 23.454 2.971 26.072 1.00 20.51 S O ANISOU 1836OH2 WAT S  51 2369 2806 2279 322 −1 −9 S O SIGUIJ 1836 OH2 WAT S  51 1 00 221 51 289 S O HETATM 1837 OH2 WAT S  52 20.163 20.835 28.950 1.0019.73 S O ANISOU 1837 OH2 WAT S  52 1831 2320 4535 −156 −248 −51 S OSIGUIJ 1837 OH2 WAT S  52 1 0 0 221 51 289 S O HETATM 1838 OH2 WAT S  5318.260 4.832 31.017 1.00 16.47 S O ANISOU 1838 OH2 WAT S  53 1722 19881893 −20 −25 −2 S O SIGUIJ 1838 OH2 WAT S  53 1 0 0 221 51 289 S OHETATM 1839 OH2 WAT S  54 3.473 1.488 41.250 1.00 15.36 S O ANISOU 1839OH2 WAT S  54 2028 1518 1768 207 409 148 S O SIGUIJ 1839 OH2 WAT S  54 10 0 221 51 289 S O HETATM 1840 OH2 WAT S  55 15.273 −6.972 16.641 1.0026.28 S O ANISOU 1840 OH2 WAT S  55 4371 3181 2970 325 235 56 S O SIGUIJ1840 OH2 WAT S  55 1 0 0 221 51 289 S O HETATM 1841 OH2 WAT S  56 4.09722.217 31.651 1.00 18.32 S O ANISOU 1841 OH2 WAT S  56 2455 2059 2064542 92 87 S O SIGUIJ 1841 OH2 WAT S  56 1 0 0 221 51 289 S O HETATM 1842OH2 WAT S  57 17.859 16.386 19.498 1.00 16.54 S O ANISOU 1842 OH2 WAT S 57 2118 2397 1880 153 666 686 S O SIGUIJ 1842 OH2 WAT S  57 1 0 0 22151 289 S O HETATM 1843 OH2 WAT S  58 3.109 −4.539 29.443 1.00 23.06 S OANISOU 1843 OH2 WAT S  58 4608 2423 2713 35 808 13 S O SIGUIJ 1843 OH2WAT S  58 1 0 0 221 51 289 S O HETATM 1844 OH2 WAT S  59 −2.538 7.34937.099 1.00 19.86 S O ANISOU 1844 OH2 WAT S  59 2079 2504 2374 −596 170179 S O SIGUIJ 1844 OH2 WAT S  59 1 0 0 221 51 289 S O HETATM 1845 OH2WAT S  60 19.442 18.113 31.002 1.00 32.60 S O ANISOU 1845 OH2 WAT S  605406 6964 4243 11 −68 0 S O SIGUIJ 1845 OH2 WAT S  60 1 0 0 221 51 289 SO HETATM 1846 OH2 WAT S  62 4.758 −5.404 30.600 1.00 24.62 S O ANISOU1846 OH2 WAT S  62 2411 3146 3148 −140 29 5 S O SIGUIJ 1846 OH2 WAT S 62 1 0 0 221 51 289 S O HETATM 1847 OH2 WAT S  63 11.832 20.865 35.3821.00 22.71 S O ANISOU 1847 OH2 WAT S  63 3516 3544 2255 −2153 −517 619 SO SIGUIJ 1847 OH2 WAT S  63 1 0 0 221 51 289 S O HETATM 1848 OH2 WAT S 64 9.886 18.217 24.619 1.00 16.50 S O ANISOU 1848 OH2 WAT S  64 19961565 2669 −88 −22 1 S O SIGUIJ 1848 OH2 WAT S  64 1 0 0 221 51 289 S OHETATM 1849 OH2 WAT S  65 17.902 6.647 49.778 1.00 24.11 S O ANISOU 1849OH2 WAT S  65 5482 2700 2275 1291 −322 −128 S O SIGUIJ 1849 OH2 WAT S 65 1 0 0 221 51 289 S O HETATM 1850 OH2 WAT S  66 3.910 −12.994 45.1121.00 25.58 S O ANISOU 1850 OH2 WAT S  66 3118 1706 5270 346 177 10 S OSIGUIJ 1850 OH2 WAT S  66 1 0 0 221 51 289 S O HETATM 1851 OH2 WAT S  6722.241 18.528 23.106 1.00 36.69 S O ANISOU 1851 OH2 WAT S  67 3190 44055377 −5 117 0 S O SIGUIJ 1851 OH2 WAT S  67 1 0 0 221 50 289 S O HETATM1852 OH2 WAT S  68 −3.052 4.627 30.518 1.00 29.98 S O ANISOU 1852 OH2WAT S  68 5803 8921 4571 −4535 −20 −291 S O SIGUIJ 1852 OH2 WAT S  68 10 0 221 50 289 S O HETATM 1853 OH2 WAT S  69 11.974 4.666 53.712 1.0019.70 S O ANISOU 1853 OH2 WAT S  69 3516 2783 2099 −55 627 −48 S OSIGUIJ 1853 OH2 WAT S  69 1 0 0 221 50 289 S O HETATM 1854 OH2 WAT S  7027.570 −6.698 38.544 1.00 27.70 S O ANISOU 1854 OH2 WAT S  70 3182 44013470 557 −13 13 S O SIGUIJ 1854 OH2 WAT S  70 1 0 0 221 50 289 S OHETATM 1855 OH2 WAT S  71 −4.331 5.240 42.885 1.00 28.52 S O ANISOU 1855OH2 WAT S  71 2834 3803 4481 311 1196 −245 S O SIGUIJ 1855 OH2 WAT S  711 0 0 221 50 289 S O HETATM 1856 OH2 WAT S  72 −1.710 13.915 40.211 1.0020.83 S O ANISOU 1856 OH2 WAT S  72 2239 2670 3203 92 −179 26 S O SIGUIJ1856 OH2 WAT S  72 1 0 0 221 50 289 S O HETATM 1857 OH2 WAT S  73 10.0419.287 14.686 1.00 23.91 S O ANISOU 1857 OH2 WAT S  73 3206 4013 2440−343 −149 13 S O SIGUIJ 1857 OH2 WAT S  73 1 0 0 221 50 289 S O HETATM1858 OH2 WAT S  74 27.415 −2.814 43.051 1.00 27.21 S O ANISOU 1858 OH2WAT S  74 2485 2794 6783 45 −1456 25 S O SIGUIJ 1858 OH2 WAT S  74 1 0 0221 50 289 S O HETATM 1859 OH2 WAT S  75 24.225 −9.992 45.971 1.00 26.90S O ANISOU 1859 OH2 WAT S  75 3281 2840 3048 63 5 1 S O SIGUIJ 1859 OH2WAT S  75 1 0 0 221 50 289 S O HETATM 1860 OH2 WAT S  76 7.451 15.58721.470 1.00 18.46 S O ANISOU 1860 OH2 WAT S  76 3159 2145 1620 190 97 15S O SIGUIJ 1860 OH2 WAT S  76 1 0 0 221 50 289 S O HETATM 1861 OH2 WAT S 77 23.079 9.316 51.019 1.00 31.41 S O ANISOU 1861 OH2 WAT S  77 72062582 3785 −1401 1671 −513 S O SIGUIJ 1861 OH2 WAT S  77 1 0 0 221 50 289S O HETATM 1862 OH2 WAT S  78 −3.582 2.710 41.526 1.00 23.55 S O ANISOU1862 OH2 WAT S  78 1798 3072 3934 −311 96 18 S O SIGUIJ 1862 OH2 WAT S 78 1 0 0 221 50 289 S O HETATM 1863 OH2 WAT S  79 9.534 −7.797 21.7041.00 22.74 S O ANISOU 1863 OH2 WAT S  79 2763 4898 1870 557 −89 −22 S OSIGUIJ 1863 OH2 WAT S  79 1 0 0 221 50 289 S O HETATM 1864 OH2 WAT S  802.971 16.345 14.945 1.00 30.00 S O ANISOU 1864 OH2 WAT S  80 3558 41334282 33 −20 1 S O SIGUIJ 1864 OH2 WAT S  80 1 0 0 221 50 289 S O HETATM1865 OH2 WAT S  81 20.740 −0.313 53.174 1.00 22.50 S O ANISOU 1865 OH2WAT S  81 3241 2437 2297 −463 −658 268 S O SIGUIJ 1865 OH2 WAT S  81 1 00 221 50 289 S O HETATM 1866 OH2 WAT S  82 22.883 −0.067 51.495 1.0027.35 S O ANISOU 1866 OH2 WAT S  82 2443 3395 2903 −569 −66 −50 S OSIGUIJ 1866 OH2 WAT S  82 1 0 0 221 50 289 S O HETATM 1867 OH2 WAT S  84−1.171 7.724 20.366 1.00 26.92 S O ANISOU 1867 OH2 WAT S  84 2753 57203097 344 −29 15 S O SIGUIJ 1867 OH2 WAT S  84 1 0 0 221 50 289 S OHETATM 1868 OH2 WAT S  85 3.600 5.966 14.955 1.00 25.46 S O ANISOU 1868OH2 WAT S  85 3254 4647 1830 1465 −70 −46 S O SIGUIJ 1868 OH2 WAT S  851 0 0 221 50 289 S O HETATM 1869 OH2 WAT S  86 32.035 8.228 33.633 1.0027.13 S O ANISOU 1869 OH2 WAT S  86 3557 4229 3973 10 −13 0 S O SIGUIJ1869 OH2 WAT S  86 1 0 0 221 50 289 S O HETATM 1870 OH2 WAT S  87 10.74424.913 28.060 1.00 29.54 S O ANISOU 1870 OH2 WAT S  87 5299 3251 4261−984 −31 20 S O SIGUIJ 1870 OH2 WAT S  87 1 0 0 221 50 289 S O HETATM1871 OH2 WAT S  88 20.299 −8.109 23.247 1.00 24.84 S O ANISOU 1871 OH2WAT S  88 4326 2753 2982 924 61 34 S O SIGUIJ 1871 OH2 WAT S  88 1 0 0221 50 289 S O HETATM 1872 OH2 WAT S  89 13.944 8.215 13.170 1.00 22.01S O ANISOU 1872 OH2 WAT S  89 2965 4174 1733 −774 −109 8 S O SIGUIJ 1872OH2 WAT S  89 1 0 0 221 50 289 S O HETATM 1873 OH2 WAT S  90 18.81815.142 31.512 1.00 19.19 S O ANISOU 1873 OH2 WAT S  90 2253 3049 1644−56 53 −1 S O SIGUIJ 1873 OH2 WAT S  90 1 0 0 221 50 289 S O HETATM 1874OH2 WAT S  91 10.160 14.327 23.218 1.00 17.24 S O ANISOU 1874 OH2 WAT S 91 2285 2044 2240 −28 0 0 S O SIGUIJ 1874 OH2 WAT S  91 1 0 0 221 50289 S O HETATM 1875 OH2 WAT S  92 19.051 2.536 18.790 1.00 22.31 S OANISOU 1875 OH2 WAT S  92 3789 2407 1997 −450 605 −159 S O SIGUIJ 1875OH2 WAT S  92 1 0 0 221 50 289 S O HETATM 1876 OH2 WAT S  93 18.31115.147 36.811 1.00 23.61 S O ANISOU 1876 OH2 WAT S  93 2272 2201 4255−624 −97 10 S O SIGUIJ 1876 OH2 WAT S  93 1 0 0 221 50 289 S O HETATM1877 OH2 WAT S  94 22.759 11.550 16.574 1.00 24.71 S O ANISOU 1877 OH2WAT S  94 3729 2674 3069 −99 46 −6 S O SIGUIJ 1877 OH2 WAT S  94 1 0 0221 50 289 S O HETATM 1878 OH2 WAT S  95 4.625 −0.920 52.854 1.00 25.59S O ANISOU 1878 OH2 WAT S  95 2602 6051 2740 1218 −27 59 S O SIGUIJ 1878OH2 WAT S  95 1 0 0 221 50 289 S O HETATM 1879 OH2 WAT S  96 28.207−6.456 34.713 1.00 24.66 S O ANISOU 1879 OH2 WAT S  96 2941 4153 8749 51−1299 59 S O SIGUIJ 1879 OH2 WAT S  96 1 0 0 221 50 289 S O HETATM 1880OH2 WAT S  97 22.260 −8.621 24.974 1.00 25.76 S O ANISOU 1880 OH2 WAT S 97 4216 2047 2584 300 −177 −28 S O SIGUIJ 1880 OH2 WAT S  97 1 0 0 22150 289 S O HETATM 1881 OH2 WAT S  98 29.377 1.424 35.670 1.00 28.05 S OANISOU 1881 OH2 WAT S  98 2756 3143 5489 −29 −1115 −15 S O SIGUIJ 1881OH2 WAT S  98 1 0 0 221 50 289 S O HETATM 1882 OH2 WAT S  99 7.97826.620 35.039 1.00 27.96 S O ANISOU 1882 OH2 WAT S  99 4287 3004 3516776 23 16 S O SIGUIJ 1882 OH2 WAT S  99 1 0 0 221 50 289 S O HETATM 1883OH2 WAT S 100 22.630 9.441 32.458 1.00 20.69 S O ANISOU 1883 OH2 WAT S100 2311 2591 2466 −17 0 0 S O SIGUIJ 1883 OH2 WAT S 100 1 0 0 221 50289 S O HETATM 1884 OH2 WAT S 101 0.044 −0.604 40.115 1.00 23.48 S OANISOU 1884 OH2 WAT S 101 4663 1966 3220 908 112 51 S O SIGUIJ 1884 OH2WAT S 101 1 0 0 221 50 289 S O HETATM 1885 OH2 WAT S 102 10.586 −14.31036.023 1.00 32.88 S O ANISOU 1885 OH2 WAT S 102 3736 3334 5679 13 374 0S O SIGUIJ 1885 OH2 WAT S 102 1 0 0 221 50 289 S O HETATM 1886 OH2 WAT S103 −0.807 17.916 30.201 1.00 25.73 S O ANISOU 1886 OH2 WAT S 103 25923349 4155 480 117 −46 S O SIGUIJ 1886 OH2 WAT S 103 1 0 0 221 50 289 S OHETATM 1887 OH2 WAT S 104 26.760 −8.913 35.163 1.00 27.66 S O ANISOU1887 OH2 WAT S 104 2555 3497 5031 791 −387 171 S O SIGUIJ 1887 OH2 WAT S104 1 0 0 221 50 289 S O HETATM 1888 OH2 WAT S 105 3.515 9.065 11.7591.00 30.62 S O ANISOU 1888 OH2 WAT S 105 3112 4092 5105 142 389 −40 S OSIGUIJ 1888 OH2 WAT S 105 1 0 0 221 50 289 S O HETATM 1889 OH2 WAT S 1066.014 6.816 50.133 1.00 22.77 S O ANISOU 1889 OH2 WAT S 106 2984 34872553 −65 64 −1 S O SIGUIJ 1889 OH2 WAT S 106 1 0 0 221 50 289 S O HETATM1890 OH2 WAT S 107 2.535 0.919 21.717 1.00 30.69 S O ANISOU 1890 OH2 WATS 107 2951 3619 3870 88 −46 5 S O SIGUIJ 1890 OH2 WAT S 107 1 0 0 221 50289 S O HETATM 1891 OH2 WAT S 108 8.473 5.739 51.277 1.00 27.33 S OANISOU 1891 OH2 WAT S 108 3033 2855 4859 3 610 12 S O SIGUIJ 1891 OH2WAT S 108 1 0 0 221 50 289 S O HETATM 1892 OH2 WAT S 109 27.074 −11.87944.074 1.00 31.97 S O ANISOU 1892 OH2 WAT S 109 6557 3884 8374 −192 1 0S O SIGUIJ 1892 OH2 WAT S 109 1 0 0 221 50 289 S O HETATM 1893 OH2 WAT S110 26.737 −0.258 45.534 1.00 24.30 S O ANISOU 1893 OH2 WAT S 110 28193015 3951 8 −466 17 S O SIGUIJ 1893 OH2 WAT S 110 1 0 0 221 50 289 S OHETATM 1894 OH2 WAT S 111 23.962 16.801 23.275 1.00 30.34 S O ANISOU1894 OH2 WAT S 111 4010 6257 3100 −2485 −7 57 S O SIGUIJ 1894 OH2 WAT S111 1 0 0 221 50 289 S O HETATM 1895 OH2 WAT S 112 16.366 −14.016 33.2501.00 31.21 S O ANISOU 1895 OH2 WAT S 112 6815 4084 4423 −1632 −105 59 SO SIGUIJ 1895 OH2 WAT S 112 1 0 0 221 50 289 S O HETATM 1896 OH2 WAT S113 31.549 3.790 28.438 1.00 29.85 S O ANISOU 1896 OH2 WAT S 113 23615373 3457 −594 487 160 S O SIGUIJ 1896 OH2 WAT S 113 1 0 0 221 50 289 SO HETATM 1897 OH2 WAT S 114 29.814 0.473 25.485 1.00 33.55 S O ANISOU1897 OH2 WAT S 114 3467 6416 4692 1851 324 −280 S O SIGUIJ 1897 OH2 WATS 114 1 0 0 221 50 289 S O HETATM 1898 OH2 WAT S 115 15.127 12.28745.057 1.00 20.18 S O ANISOU 1898 OH2 WAT S 115 2358 2101 2652 −13 −4 0S O SIGUIJ 1898 OH2 WAT S 115 1 0 0 221 50 289 S O HETATM 1899 OH2 WAT S116 25.755 −5.365 27.616 1.00 27.02 S O ANISOU 1899 OH2 WAT S 116 38594146 2556 39 281 −27 S O SIGUIJ 1899 OH2 WAT S 116 1 0 0 221 50 289 S OHETATM 1900 OH2 WAT S 117 2.661 19.940 22.804 1.00 28.19 S O ANISOU 1900OH2 WAT S 117 2612 4405 4384 427 −139 32 S O SIGUIJ 1900 OH2 WAT S 117 10 0 221 50 289 S O HETATM 1901 OH2 WAT S 118 13.816 10.501 27.860 1.0018.47 S O ANISOU 1901 OH2 WAT S 118 2713 2171 1862 −163 9 −2 S O SIGUIJ1901 OH2 WAT S 118 1 0 0 221 50 289 S O HETATM 1902 OH2 WAT S 119 26.259−0.965 25.298 1.00 33.83 S O ANISOU 1902 OH2 WAT S 119 3054 7527 4940−751 504 127 S O SIGUIJ 1902 OH2 WAT S 119 1 0 0 221 50 289 S O HETATM1903 OH2 WAT S 120 11.223 23.743 16.870 1.00 33.09 S O ANISOU 1903 OH2WAT S 120 6540 2820 4675 −1098 −79 33 S O SIGUIJ 1903 OH2 WAT S 120 1 00 221 50 289 S O HETATM 1904 OH2 WAT S 121 −0.480 7.799 26.995 1.0026.19 S O ANISOU 1904 OH2 WAT S 121 3214 4175 2071 163 −451 −7 S OSIGUIJ 1904 OH2 WAT S 121 1 0 0 221 50 289 S O HETATM 1905 OH2 WAT S 1222.362 15.205 44.578 1.00 27.82 S O ANISOU 1905 OH2 WAT S 122 5512 23054024 −230 173 −21 S O SIGUIJ 1905 OH2 WAT S 122 1 0 0 221 50 289 S OHETATM 1906 OH2 WAT S 123 19.715 7.754 50.940 1.00 25.17 S O ANISOU 1906OH2 WAT S 123 3519 3788 2747 −14 107 1 S O SIGUIJ 1906 OH2 WAT S 123 1 00 221 50 289 S O HETATM 1907 OH2 WAT S 124 2.758 18.725 16.752 1.0034.08 S O ANISOU 1907 OH2 WAT S 124 5908 6912 4121 12 −107 1 S O SIGUIJ1907 OH2 WAT S 124 1 0 0 221 50 289 S O HETATM 1908 OH2 WAT S 125 −4.642−10.188 42.639 1.00 29.52 S O ANISOU 1908 OH2 WAT S 125 2512 4249 9593−641 1917 396 S O SIGUIJ 1908 OH2 WAT S 125 1 0 0 221 50 289 S O HETATM1909 OH2 WAT S 126 1.240 18.510 38.272 1.00 27.99 S O ANISOU 1909 OH2WAT S 126 4172 2933 2552 −57 889 −32 S O SIGUIJ 1909 OH2 WAT S 126 1 0 0221 50 289 S O HETATM 1910 OH2 WAT S 127 3.642 −7.543 31.958 1.00 27.77S O ANISOU 1910 OH2 WAT S 127 3242 3568 3779 −1225 −131 −168 S O SIGUIJ1910 OH2 WAT S 127 1 0 0 221 50 289 S O HETATM 1911 OH2 WAT S 128 −2.003−7.145 36.395 1.00 36.40 S O ANISOU 1911 OH2 WAT S 128 4151 5058 5863−12 49 0 S O SIGUIJ 1911 OH2 WAT S 128 1 0 0 221 50 289 S O HETATM 1912OH2 WAT S 129 15.145 −8.406 27.073 1.00 37.08 S O ANISOU 1912 OH2 WAT S129 6125 6305 3951 3848 −145 −185 S O SIGUIJ 1912 OH2 WAT S 129 1 0 0221 50 289 S O HETATM 1913 OH2 WAT S 130 27.252 15.441 28.847 1.00 38.58S O ANISOU 1913 OH2 WAT S 130 7244 4494 10213 95 48 0 S O SIGUIJ 1913OH2 WAT S 130 1 0 0 221 50 289 S O HETATM 1914 OH2 WAT S 131 24.590−4.578 24.926 1.00 35.10 S O ANISOU 1914 OH2 WAT S 131 3086 6214 4364997 45 −23 S O SIGUIJ 1914 OH2 WAT S 131 1 0 0 221 50 289 S O HETATM1915 OH2 WAT S 132 26.779 10.309 19.245 1.00 31.56 S O ANISOU 1915 OH2WAT S 132 3055 7679 5170 1664 139 −74 S O SIGUIJ 1915 OH2 WAT S 132 1 00 221 50 289 S O HETATM 1916 OH2 WAT S 133 0.533 −7.125 45.253 1.0027.88 S O ANISOU 1916 OH2 WAT S 133 2994 2259 3593 −212 48 3 S O SIGUIJ1916 OH2 WAT S 133 1 0 0 221 50 289 S O HETATM 1917 OH2 WAT S 134 16.753−10.311 29.928 1.00 34.28 S O ANISOU 1917 OH2 WAT S 134 4945 7839 2779−415 −1740 −230 S O SIGUIJ 1917 OH2 WAT S 134 1 0 0 221 50 289 S OHETATM 1918 OH2 WAT S 135 10.504 −11.853 51.167 1.00 25.02 S O ANISOU1918 OH2 WAT S 135 5148 2692 3373 −1536 −817 494 S O SIGUIJ 1918 OH2 WATS 135 1 0 0 221 50 289 S O HETATM 1919 OH2 WAT S 136 15.253 19.09016.547 1.00 35.54 S O ANISOU 1919 OH2 WAT S 136 6539 6105 2770 13 478 5S O SIGUIJ 1919 OH2 WAT S 136 1 0 0 221 50 289 S O HETATM 1920 OH2 WAT S137 24.070 15.576 28.300 1.00 39.96 S O ANISOU 1920 OH2 WAT S 137 60823159 8207 150 −17 0 S O SIGUIJ 1920 OH2 WAT S 137 1 0 0 221 50 289 S OHETATM 1921 OH2 WAT S 138 19.951 −7.890 49.428 1.00 37.63 S O ANISOU1921 OH2 WAT S 138 6820 3803 3909 1919 69 39 S O SIGUIJ 1921 OH2 WAT S138 1 0 0 221 50 289 S O HETATM 1922 OH2 WAT S 139 9.825 −10.874 30.0241.00 24.32 S O ANISOU 1922 OH2 WAT S 139 4437 1727 3182 −42 382 −3 S OSIGUIJ 1922 OH2 WAT S 139 1 0 0 221 50 289 S O HETATM 1923 OH2 WAT S 14014.562 14.178 16.243 1.00 30.34 S O ANISOU 1923 OH2 WAT S 140 5368 37193000 −1110 560 −266 S O SIGUIJ 1923 OH2 WAT S 140 1 0 0 221 50 289 S OHETATM 1924 OH2 WAT S 141 9.307 13.549 16.592 1.00 30.74 S O ANISOU 1924OH2 WAT S 141 4656 5144 4124 48 −3 0 S O SIGUIJ 1924 OH2 WAT S 141 1 0 0221 49 289 S O HETATM 1925 OH2 WAT S 142 0.546 21.352 27.878 1.00 40.45S O ANISOU 1925 OH2 WAT S 142 9491 3460 8370 1133 −6 −3 S O SIGUIJ 1925OH2 WAT S 142 1 0 0 221 49 289 S O HETATM 1926 OH2 WAT S 143 −1.88514.390 46.062 1.00 29.21 S O ANISOU 1926 OH2 WAT S 143 3516 3899 2996 3839 −1 S O SIGUIJ 1926 OH2 WAT S 143 1 0 0 221 49 289 S O HETATM 1927 OH2WAT S 144 29.346 −6.151 41.426 1.00 41.53 S O ANISOU 1927 OH2 WAT S 1443285 8590 8848 929 1170 −193 S O SIGUIJ 1927 OH2 WAT S 144 1 0 0 221 49289 S O HETATM 1928 OH2 WAT S 145 29.449 −1.201 37.125 1.00 33.69 S OANISOU 1928 OH2 WAT S 145 2299 13945 5181 1681 −132 46 S O SIGUIJ 1928OH2 WAT S 145 1 0 0 221 49 289 S O HETATM 1929 OH2 WAT S 146 25.2520.908 49.035 1.00 29.41 S O ANISOU 1929 OH2 WAT S 146 2514 6062 45101324 −138 67 S O SIGUIJ 1929 OH2 WAT S 146 1 0 0 221 49 289 S O HETATM1930 OH2 WAT S 147 2.465 1.781 52.221 1.00 25.79 S O ANISOU 1930 OH2 WATS 147 4627 3968 2707 6 −449 −2 S O SIGUIJ 1930 OH2 WAT S 147 1 0 0 22149 289 S O HETATM 1931 OH2 WAT S 148 −4.135 10.402 43.978 1.00 33.44 S OANISOU 1931 OH2 WAT S 148 3655 7568 7772 2975 −323 200 S O SIGUIJ 1931OH2 WAT S 148 1 0 0 221 49 289 S O HETATM 1932 OH2 WAT S 149 17.550−1.360 16.721 1.00 26.03 S O ANISOU 1932 OH2 WAT S 149 5814 3014 2319293 1493 103 S O SIGUIJ 1932 OH2 WAT S 149 1 0 0 221 49 289 S O HETATM1933 OH2 WAT S 150 10.868 14.790 18.228 1.00 26.66 S O ANISOU 1933 OH2WAT S 150 3764 3047 2718 112 −180 −23 S O SIGUIJ 1933 OH2 WAT S 150 1 00 221 49 289 S O HETATM 1934 OH2 WAT S 151 1.010 −10.401 38.943 1.0040.44 S O ANISOU 1934 OH2 WAT S 151 2459 2034 3405 −95 −126 4 S O SIGUIJ1934 OH2 WAT S 151 1 0 0 221 49 289 S O HETATM 1935 OH2 WAT S 152 30.616−13.418 38.615 1.00 34.81 S O ANISOU 1935 OH2 WAT S 152 8399 3393 10988−717 −27 −2 S O SIGUIJ 1935 OH2 WAT S 152 1 0 0 221 49 289 S O HETATM1936 OH2 WAT S 153 24.409 3.497 23.403 1.00 40.31 S O ANISOU 1936 OH2WAT S 153 5220 10991 3367 4730 −16 −70 S O SIGUIJ 1936 OH2 WAT S 153 1 00 221 49 289 S O HETATM 1937 OH2 WAT S 154 21.557 7.062 27.654 1.0028.84 S O ANISOU 1937 OH2 WAT S 154 3016 2992 2883 1 5 0 S O SIGUIJ 1937OH2 WAT S 154 1 0 0 221 49 289 S O HETATM 1938 OH2 WAT S 155 20.51718.633 25.054 1.00 30.26 S O ANISOU 1938 OH2 WAT S 155 2750 4489 4630−321 −103 −18 S O SIGUIJ 1938 OH2 WAT S 155 1 0 0 221 49 289 S O HETATM1939 OH2 WAT S 156 32.648 4.297 32.274 1.00 37.94 S O ANISOU 1939 OH2WAT S 156 3269 8129 5917 181 −262 14 S O SIGUIJ 1939 OH2 WAT S 156 1 0 0221 49 289 S O HETATM 1940 OH2 WAT S 157 21.979 13.016 14.583 1.00 35.88S O ANISOU 1940 OH2 WAT S 157 9146 5044 3682 317 1657 104 S O SIGUIJ1940 OH2 WAT S 157 1 0 0 221 49 289 S O HETATM 1941 OH2 WAT S 158 6.095−7.842 18.423 1.00 34.85 S O ANISOU 1941 OH2 WAT S 158 12566 3609 4280163 −318 −6 S O SIGUIJ 1941 OH2 WAT S 158 1 0 0 221 49 289 S O HETATM1942 OH2 WAT S 159 26.591 −4.927 36.071 1.00 29.60 S O ANISOU 1942 OH2WAT S 159 4378 4005 3346 −44 −89 7 S O SIGUIJ 1942 OH2 WAT S 159 1 0 0221 49 289 S O HETATM 1943 OH2 WAT S 160 5.561 0.764 54.769 1.00 30.77 SO ANISOU 1943 OH2 WAT S 160 2598 3822 2614 932 −4 10 S O SIGUIJ 1943 OH2WAT S 160 1 0 0 221 49 289 S O HETATM 1944 OH2 WAT S 161 10.527 25.60925.108 1.00 34.60 S O ANISOU 1944 OH2 WAT S 161 3770 3075 7386 10 −1730−25 S O SIGUIJ 1944 OH2 WAT S 161 1 0 0 221 49 289 S O HETATM 1945 OH2WAT S 162 3.585 27.472 24.727 1.00 37.60 S O ANISOU 1945 OH2 WAT S 1625160 6221 7339 −23 −124 −2 S O SIGUIJ 1945 OH2 WAT S 162 1 0 0 221 49289 S O HETATM 1946 OH2 WAT S 163 −3.314 −0.083 44.414 1.00 33.32 S OANISOU 1946 OH2 WAT S 163 2250 7193 5469 904 −129 29 S O SIGUIJ 1946 OH2WAT S 163 1 0 0 221 49 289 S O HETATM 1947 OH2 WAT S 165 20.321 8.94248.820 1.00 9.64 S O ANISOU 1947 OH2 WAT S 165 3678 3212 2252 −60 140−12 S O SIGUIJ 1947 OH2 WAT S 165 1 0 0 221 49 289 S O HETATM 1948 OH2WAT S 166 16.533 7.447 53.478 1.00 9.64 S O ANISOU 1948 OH2 WAT S 1663421 5345 3498 −1663 12 27 S O SIGUIJ 1948 OH2 WAT S 166 1 0 0 221 49289 S O HETATM 1949 OH2 WAT S 167 6.384 13.286 44.630 1.00 9.64 S OANISOU 1949 OH2 WAT S 167 4095 2912 2148 1211 −629 −376 S O SIGUIJ 1949OH2 WAT S 167 1 0 0 221 49 289 S O HETATM 1950 OH2 WAT S 168 15.58614.651 46.353 1.00 9.64 S O ANISOU 1950 OH2 WAT S 168 5956 2789 3140−1976 788 −443 S O SIGUIJ 1950 OH2 WAT S 168 1 0 0 221 49 289 S O HETATM1951 OH2 WAT S 169 17.717 14.045 44.656 1.00 9.64 S O ANISOU 1951 OH2WAT S 169 2696 3803 3222 −469 −12 −7 S O SIGUIJ 1951 OH2 WAT S 169 1 0 0221 49 289 S O HETATM 1952 OH2 WAT S 170 11.975 11.416 52.995 1.00 9.64S O ANISOU 1952 OH2 WAT S 170 4141 3516 3042 −26 −61 2 S O SIGUIJ 1952OH2 WAT S 170 1 0 0 221 49 289 S O HETATM 1953 OH2 WAT S 171 −8.8324.580 35.128 1.00 9.64 S O ANISOU 1953 OH2 WAT S 171 3442 5617 4705 1720401 −335 S O SIGUIJ 1953 OH2 WAT S 171 1 0 0 221 49 289 S O HETATM 1954OH2 WAT S 172 −4.277 −4.060 36.933 1.00 9.64 S O ANISOU 1954 OH2 WAT S172 3880 2781 5563 −10 −45 0 S O SIGUIJ 1954 OH2 WAT S 172 1 0 0 221 49289 S O HETATM 1955 OH2 WAT S 173 −0.557 −0.253 30.091 1.00 9.64 S OANISOU 1955 OH2 WAT S 173 4876 8675 2710 779 −714 −21 S O SIGUIJ 1955OH2 WAT S 173 1 0 0 221 49 289 S O HETATM 1956 OH2 WAT S 174 −1.0052.812 28.885 1.00 9.64 S O ANISOU 1956 OH2 WAT S 174 2929 6755 3085 −2523 2 S O SIGUIJ 1956 OH2 WAT S 174 1 0 0 221 49 289 S O HETATM 1957 OH2WAT S 175 2.618 2.639 29.286 1.00 9.64 S O ANISOU 1957 OH2 WAT S 1752571 3346 2427 −193 −6 4 S O SIGUIJ 1957 OH2 WAT S 175 1 0 0 221 49 289S O HETATM 1958 OH2 WAT S 176 −6.600 7.509 35.036 1.00 9.64 S O ANISOU1958 OH2 WAT S 176 2597 3342 6658 −80 845 24 S O SIGUIJ 1958 OH2 WAT S176 1 0 0 221 49 289 S O HETATM 1959 OH2 WAT S 177 −0.477 17.088 36.9111.00 9.64 S O ANISOU 1959 OH2 WAT S 177 2189 3076 4218 −3 153 0 S OSIGUIJ 1959 OH2 WAT S 177 1 0 0 221 49 289 S O HETATM 1960 OH2 WAT S 178−1.260 11.427 27.528 1.00 9.64 S O ANISOU 1960 OH2 WAT S 178 2773 49693125 419 14 −9 S O SIGUIJ 1960 OH2 WAT S 178 1 0 0 221 49 289 S O HETATM1961 OH2 WAT S 179 −0.390 18.740 34.942 1.00 9.64 S O ANISOU 1961 OH2WAT S 179 2232 2541 2884 −14 9 0 S O SIGUIJ 1961 OH2 WAT S 179 1 0 0 22149 289 S O HETATM 1962 OH2 WAT S 180 −3.823 8.680 29.774 1.00 9.64 S OANISOU 1962 OH2 WAT S 180 5318 4474 2845 −21 −757 15 S O SIGUIJ 1962 OH2WAT S 180 1 0 0 221 49 289 S O HETATM 1963 OH2 WAT S 181 −0.781 16.01942.114 1.00 9.64 S O ANISOU 1963 OH2 WAT S 181 1433 1370 1665 12 407−109 S O SIGUIJ 1963 OH2 WAT S 181 1 0 0 221 49 289 S O HETATM 1964 OH2WAT S 182 −1.833 14.757 37.559 1.00 9.64 S O ANISOU 1964 OH2 WAT S 1822296 2695 3332 99 −89 14 S O SIGUIJ 1964 OH2 WAT S 182 1 0 0 221 49 289S O HETATM 1965 OH2 WAT S 183 0.603 17.701 32.591 1.00 9.64 S O ANISOU1965 OH2 WAT S 183 2203 1894 3016 325 −284 −36 S O SIGUIJ 1965 OH2 WAT S183 1 0 0 221 49 289 S O HETATM 1966 OH2 WAT S 184 25.865 12.353 35.3631.00 16.02 S O ANISOU 1966 OH2 WAT S 184 3641 5196 6549 185 434 −39 S OSIGUIJ 1966 OH2 WAT S 184 1 0 0 221 49 289 S O HETATM 1967 OH2 WAT S 18521.844 14.030 33.136 1.00 16.02 S O ANISOU 1967 OH2 WAT S 185 4516 43864212 −31 3 −1 S O SIGUIJ 1967 OH2 WAT S 185 1 0 0 221 49 289 S O HETATM1968 OH2 WAT S 186 −2.383 11.857 46.800 1.00 21.37 S O ANISOU 1968 OH2WAT S 186 4014 3408 2846 −9 1102 −20 S O SIGUIJ 1968 OH2 WAT S 186 1 0 0221 49 289 S O HETATM 1969 OH2 WAT S 187 −0.771 10.542 48.286 1.00 21.37S O ANISOU 1969 OH2 WAT S 187 3450 4573 5571 570 2454 −643 S O SIGUIJ1969 OH2 WAT S 187 1 0 0 221 49 289 S O HETATM 1970 OH2 WAT S 188 2.33612.093 46.980 1.00 21.37 S O ANISOU 1970 OH2 WAT S 188 7535 3031 48552228 335 199 S O SIGUIJ 1970 OH2 WAT S 188 1 0 0 221 49 289 S O HETATM1971 OH2 WAT S 189 5.725 8.697 49.067 1.00 21.37 S O ANISOU 1971 OH2 WATS 189 4279 5874 5746 223 −22 3 S O SIGUIJ 1971 OH2 WAT S 189 1 0 0 22149 289 S O HETATM 1972 OH2 WAT S 190 0.753 1.655 54.193 1.00 21.37 S OANISOU 1972 OH2 WAT S 190 3706 5034 3101 120 −22 −1 S O SIGUIJ 1972 OH2WAT S 190 1 0 0 221 49 289 S O HETATM 1973 OH2 WAT S 191 19.317 3.22756.607 1.00 17.18 S O ANISOU 1973 OH2 WAT S 191 7181 7861 2353 7 481 −2S O SIGUIJ 1973 OH2 WAT S 191 1 0 0 221 49 289 S O HETATM 1974 OH2 WAT S192 26.731 −5.241 46.724 1.00 17.18 S O ANISOU 1974 OH2 WAT S 192 27246561 5059 995 −414 135 S O SIGUIJ 1974 OH2 WAT S 192 1 0 0 221 49 289 SO HETATM 1975 OH2 WAT S 193 18.256 −2.444 55.645 1.00 17.18 S O ANISOU1975 OH2 WAT S 193 1320 2103 1091 −559 −7 29 S O SIGUIJ 1975 OH2 WAT S193 1 0 0 221 49 289 S O HETATM 1976 OH2 WAT S 194 20.237 −5.102 53.7961.00 17.18 S O ANISOU 1976 OH2 WAT S 194 3347 3939 3483 −19 1 0 S OSIGUIJ 1976 OH2 WAT S 194 1 0 0 221 49 289 S O HETATM 1977 OH2 WAT S 19521.094 −6.781 51.353 1.00 17.18 S O ANISOU 1977 OH2 WAT S 195 7088 46784621 334 −2 0 S O SIGUIJ 1977 OH2 WAT S 195 1 0 0 221 49 289 S O HETATM1978 OH2 WAT S 196 21.448 −10.306 48.745 1.00 17.18 S O ANISOU 1978 OH2WAT S 196 4343 3129 4025 247 1 1 S O SIGUIJ 1978 OH2 WAT S 196 1 0 0 22149 289 S O HETATM 1979 OH2 WAT S 197 2.024 −13.128 46.308 1.00 25.58 S OANISOU 1979 OH2 WAT S 197 9217 4744 3533 −710 445 −62 S O SIGUIJ 1979OH2 WAT S 197 1 0 0 221 49 289 S O HETATM 1980 OH2 WAT S 198 −1.668−8.796 47.162 1.00 25.58 S O ANISOU 1980 OH2 WAT S 198 6335 5284 3131 −6−1760 8 S O SIGUIJ 1980 OH2 WAT S 198 1 0 0 221 49 289 S O HETATM 1981OH2 WAT S 199 6.598 −13.515 48.535 1.00 25.58 S O ANISOU 1981 OH2 WAT S199 5435 4232 7877 −124 154 −4 S O SIGUIJ 1981 OH2 WAT S 199 1 0 0 22149 289 S O HETATM 1982 OH2 WAT S 200 6.414 −10.714 49.635 1.00 25.58 S OANISOU 1982 OH2 WAT S 200 2698 3540 4106 −272 387 92 S O SIGUIJ 1982 OH2WAT S 200 1 0 0 221 49 289 S O HETATM 1983 OH2 WAT S 201 12.536 −12.34930.216 1.00 24.32 S O ANISOU 1983 OH2 WAT S 201 4851 4539 6835 1 197 0 SO SIGUIJ 1983 OH2 WAT S 201 1 0 0 221 49 289 S O HETATM 1984 OH2 WAT S202 8.989 −10.878 25.331 1.00 24.32 S O ANISOU 1984 OH2 WAT S 202 40474487 7218 −34 −219 −10 S O SIGUIJ 1984 OH2 WAT S 202 1 0 0 221 49 289 SO HETATM 1985 OH2 WAT S 203 12.685 −11.368 33.176 1.00 24.32 S O ANISOU1985 OH2 WAT S 203 4501 2699 4335 953 19 31 S O SIGUIJ 1985 OH2 WAT S203 1 0 0 221 49 289 S O HETATM 1986 OH2 WAT S 204 10.361 −9.570 33.5731.00 24.32 S O ANISOU 1986 OH2 WAT S 204 2303 2590 1842 103 −2 0 S OSIGUIJ 1986 OH2 WAT S 204 1 0 0 221 49 289 S O HETATM 1987 OH2 WAT S 20516.739 2.916 16.744 1.00 30.34 S O ANISOU 1987 OH2 WAT S 205 3417 22955206 −90 −1644 120 S O SIGUIJ 1987 OH2 WAT S 205 1 0 0 221 49 289 S OHETATM 1988 OH2 WAT S 206 12.807 15.979 16.650 1.00 30.34 S O ANISOU1988 OH2 WAT S 206 4899 5487 2438 −2 −236 0 S O SIGUIJ 1988 OH2 WAT S206 1 0 0 221 49 289 S O HETATM 1989 OH2 WAT S 207 13.046 13.246 13.9911.00 30.34 S O ANISOU 1989 OH2 WAT S 207 5929 2552 3354 −110 278 −11 S OSIGUIJ 1989 OH2 WAT S 207 1 0 0 221 49 289 S O HETATM 1990 OH2 WAT S 20812.133 10.659 13.167 1.00 30.34 S O ANISOU 1990 OH2 WAT S 208 4112 44042364 −13 −814 −37 S O SIGUIJ 1990 OH2 WAT S 208 1 0 0 221 49 289 S OHETATM 1991 OH2 WAT S 209 −0.469 4.967 16.910 1.00 30.69 S O ANISOU 1991OH2 WAT S 209 3322 6694 5003 811 −115 40 S O SIGUIJ 1991 OH2 WAT S 209 10 0 221 49 289 S O HETATM 1992 OH2 WAT S 210 1.757 3.180 22.914 1.0030.69 S O ANISOU 1992 OH2 WAT S 210 2424 4344 2706 −728 −30 −35 S OSIGUIJ 1992 OH2 WAT S 210 1 0 0 221 49 289 S O HETATM 1993 OH2 WAT S 2112.523 1.306 24.182 1.00 30.69 S O ANISOU 1993 OH2 WAT S 211 4403 46727372 −11 258 5 S O SIGUIJ 1993 OH2 WAT S 211 1 0 0 221 49 289 S O HETATM1994 OH2 WAT S 212 7.074 −5.418 21.373 1.00 30.69 S O ANISOU 1994 OH2WAT S 212 4232 5911 2097 −598 −394 −10 S O SIGUIJ 1994 OH2 WAT S 212 1 00 221 49 289 S O HETATM 1995 N1 INH I  1 16.972 12.024 36.885 1.00 10.95I N ANISOU 1995 N1 INH I  1 1228 1259 1389 −2 2 0 I N SIGUIJ 1995 N1 INHI  1 1 0 0 221 57 289 I N HETATM 1996 C2 INH I  1 16.470 11.815 38.2551.00 10.80 I C ANISOU 1996 C2 INH I  1 1194 1175 1389 −1 −15 0 I CSIGUIJ 1996 C2 INH I  1 1 0 0 221 67 290 I C HETATM 1997 C4 INH I  117.773 11.451 38.995 1.00 10.95 I C ANISOU 1997 C4 INH I  1 1273 15091573 70 −120 29 I C SIGUIJ 1997 C4 INH I  1 1 0 0 221 67 290 I C HETATM1998 C7 INH I  1 18.620 10.789 37.920 1.00 11.54 I C ANISOU 1998 C7 INHI  1 1340 1489 1655 20 −33 3 I C SIGUIJ 1998 C7 INH I  1 1 0 0 221 67290 I C HETATM 1999 C10 INH I  1 18.421 11.778 36.767 1.00 11.19 I CANISOU 1999 C10 INH I  1 1236 1496 1637 47 17 −2 I C SIGUIJ 1999 C10 INHI  1 1 0 0 221 66 290 I C HETATM 2000 C13 INH I  1 15.856 13.099 38.8591.00 11.37 I C ANISOU 2000 C13 INH I  1 1202 1164 1456 −2 −7 0 I CSIGUIJ 2000 C13 INH I  1 1 0 0 221 66 290 I C HETATM 2001 O14 INH I  116.080 14.251 38.328 1.00 11.37 I O ANISOU 2001 O14 INH I  1 1368 11671474 −42 12 1 I O SIGUIJ 2001 O14 INH I  1 1 0 0 221 49 289 I O HETATM2002 N15 INH I  1 15.122 12.935 39.926 1.00 11.94 I N ANISOU 2002 N15INH I  1 1164 1192 1434 4 −35 3 I N SIGUIJ 2002 N15 INH I  1 1 0 0 22157 289 I N HETATM 2003 C17 INH I  1 14.496 14.072 40.624 1.00 13.70 I CANISOU 2003 C17 INH I  1 1554 1302 1643 137 95 −44 I C SIGUIJ 2003 C17INH I  1 1 0 0 221 66 290 I C HETATM 2004 C20 INH I  1 15.528 14.72241.570 1.00 15.91 I C ANISOU 2004 C20 INH I  1 1958 1461 2142 106 −328−92 I C SIGUIJ 2004 C20 INH I  1 1 0 0 221 66 290 I C HETATM 2005 C23INH I  1 14.867 15.933 42.215 1.00 17.69 I C ANISOU 2005 C23 INH I  12620 1616 2462 346 −92 −131 I C SIGUIJ 2005 C23 INH I  1 1 0 0 221 66290 I C HETATM 2006 C24 INH I  1 15.144 17.215 41.667 1.00 19.23 I CANISOU 2006 C24 INH I  1 4714 1737 3191 128 424 45 I C SIGUIJ 2006 C24INH I  1 1 0 0 221 66 290 I C HETATM 2007 C26 INH I  1 14.536 18.41842.262 1.00 20.20 I C ANISOU 2007 C26 INH I  1 4777 1821 3026 276 191 22I C SIGUIJ 2007 C26 INH I  1 1 0 0 221 66 290 I C HETATM 2008 C28 INH I 1 13.661 18.283 43.403 1.00 20.78 I C ANISOU 2008 C28 INH I  1 36203711 2333 25 −722 47 I C SIGUIJ 2008 C28 INH I  1 1 0 0 221 66 290 I CHETATM 2009 C29 INH I  1 13.379 16.967 43.956 1.00 20.05 I C ANISOU 2009C29 INH I  1 3118 3598 2514 417 −58 −19 I C SIGUIJ 2009 C29 INH I  1 1 00 221 66 290 I C HETATM 2010 C31 INH I  1 13.993 15.794 43.341 1.0018.98 I C ANISOU 2010 C31 INH I  1 2740 3474 2538 193 −9 −4 I C SIGUIJ2010 C31 INH I  1 1 0 0 221 66 290 I C HETATM 2011 O33 INH I  1 13.06419.413 44.006 1.00 22.11 I O ANISOU 2011 O33 INH I  1 4114 3733 2949 13−204 −7 I O SIGUIJ 2011 O33 INH I  1 1 0 0 221 49 289 I O HETATM 2012C34 INH I  1 12.177 19.459 45.137 1.00 22.69 I C ANISOU 2012 C34 INH I 1 4370 5531 3098 125 −9 0 I C SIGUIJ 2012 C34 INH I  1 1 0 0 221 66 290I C HETATM 2013 C38 INH I  1 16.126 12.284 35.849 1.00 10.52 I C ANISOU2013 C38 INH I  1 1219 1235 1370 0 14 0 I C SIGUIJ 2013 C38 INH I  1 1 00 221 66 290 I C HETATM 2014 O39 INH I  1 14.881 12.259 36.053 1.0010.62 I O ANISOU 2014 O39 INH I  1 1229 1126 1282 7 −1 0 I O SIGUIJ 2014O39 INH I  1 1 0 0 221 49 289 I O HETATM 2015 N40 INH I  1 16.626 12.47834.625 1.00 11.20 I N ANISOU 2015 N40 INH I  1 1246 1379 1379 −35 27 7 IN SIGUIJ 2015 N40 INH I  1 1 0 0 221 57 289 I N HETATM 2016 C42 INH I  115.778 12.641 33.479 1.00 11.10 I C ANISOU 2016 C42 INH I  1 1317 13191413 0 −13 −1 I C SIGUIJ 2016 C42 INH I  1 1 0 0 221 66 290 I C HETATM2017 C45 INH I  1 15.690 14.043 32.901 1.00 11.46 I C ANISOU 2017 C45INH I  1 1197 1324 1481 −13 0 0 I C SIGUIJ 2017 C45 INH I  1 1 0 0 22166 290 I C HETATM 2018 C46 INH I  1 15.144 14.214 31.570 1.00 11.99 I CANISOU 2018 C46 INH I  1 1089 1484 1477 −6 44 1 I C SIGUIJ 2018 C46 INHI  1 1 0 0 221 66 290 I C HETATM 2019 C47 INH I  1 15.066 15.581 31.0021.00 12.32 I C ANISOU 2019 C47 INH I  1 1379 1478 1545 −1 −1 0 I CSIGUIJ 2019 C47 INH I  1 1 0 0 221 66 290 I C HETATM 2020 C48 INH I  115.523 16.707 31.785 1.00 12.16 I C ANISOU 2020 C48 INH I  1 1634 15141574 −102 2 −2 I C SIGUIJ 2020 C48 INH I  1 1 0 0 221 66 290 I C HETATM2021 C50 INH I  1 16.050 16.497 33.100 1.00 12.60 I C ANISOU 2021 C50INH I  1 1895 1427 1637 −229 −110 62 I C SIGUIJ 2021 C50 INH I  1 1 0 0221 66 290 I C HETATM 2022 C52 INH I  1 16.141 15.172 33.661 1.00 12.30I C ANISOU 2022 C52 INH I  1 1628 1403 1484 −201 3 −3 I C SIGUIJ 2022C52 INH I  1 1 0 0 221 66 290 I C HETATM 2023 C54 INH I  1 14.532 15.78929.716 1.00 12.51 I C ANISOU 2023 C54 INH I  1 1399 1694 1538 57 4 −1 IC SIGUIJ 2023 C54 INH I  1 1 0 0 221 66 290 I C HETATM 2024 C56 INH I  114.064 14.679 28.954 1.00 12.49 I C ANISOU 2024 C56 INH I  1 1561 17081524 −7 0 0 I C SIGUIJ 2024 C56 INH I  1 1 0 0 221 66 290 I C HETATM2025 C58 INH I  1 14.145 13.345 29.492 1.00 12.43 I C ANISOU 2025 C58INH I  1 1302 1698 1494 −38 7 1 I C SIGUIJ 2025 C58 INH I  1 1 0 0 22166 290 I C HETATM 2026 C60 INH I  1 14.676 13.131 30.768 1.00 12.08 I CANISOU 2026 C60 INH I  1 1315 1526 1491 −89 6 3 I C SIGUIJ 2026 C60 INHI  1 1 0 0 221 66 290 I C END

Example 1 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(2-pyridin-3-yl-ethyl)-amide] A) 7-Chloro-naphthalene-1-carboxylicacid methyl ester

A mixture of 50 ml of methyl 2-furoate and 400 ml of chlorobenzene isstirred at 0° for 30 minutes, at RT for 1.5 hours and at 100° for 16hours. 121 g of anhydrous AlCl₃ are added by portion at 0°. The solutionobtained is cooled, poured in an ice-bath and stirred for 30 minutesbefore extraction of the aq. phase with ether. The organic phaseobtained is washed with aq. 10% NaHCO₃ solution and brine, dried andsolvent is evaporated. The residue obtained is purified by flashchromatography on silica gel (eluent: cyclohexane/EtOAc 99/1 to 95/5) toobtain the title compound.

B) (7-Chloro-naphthalen-1-yl)-methanol

A 0.7M diisobutylaluminium hydride solution in CH₂Cl₂ is added dropwiseat −78° to 22 g of 7-chloro-naphthalene-1-carboxylic acid methyl esterin CH₂Cl₂. After stirring at −78° for 1 hour, the mixture obtained iswarmed up to 0°, quenched with aq. 10% sodium tartrate solution andstirred for further few minutes. The organic phase obtained isseparated, washed with brine, dried and solvent is evaporated. Theresidue obtained is purified by flash chromatography on silica gel(eluent: cyclohexane/EtOAc 8/1 to 4/1) and the title compound isobtained.

MS: 175 [M−H2O+H]+ TLC, Rf (cyclohexane/EtOAc 3/1)=0.3

C) 1-Azidomethyl-7-chloro-naphthalene

1.52 ml of Diphenylphosphoryl azide and 1.10 ml of1,8-diazabicyclo[5.4.0]undec-7-ene are added to 1.3 g of(7-Chloro-naphthalen-1-yl)-methanol in 18 ml of toluene. The mixtureobtained is stirred at rt for 1 hour, washed with brine, the organicphase is dried and solvent is evaporated. The residue obtained ispurified by flash chromatography on silica gel (eluent:cyclohexane/EtOAc 99/1) to yield the title compound.

TLC, Rf (cyclohexane/EtOAc 99/1)=0.333

D) C-(7-Chloro-naphthalen-1-yl)-methylamine hydrochloride

1.24 g of Triphenylphosphine and 410 μl of H2O are added to 998 mg of1-azidomethyl-7-chloro-naphthalene in 20 ml of THF. The mixture obtainedis stirred at 50° for 5 hours and solvent is evaporated. The residueobtained is acidified with aq. 1N HCl solution and extracted with EtOAc.The aq. phase obtained is basified with aq. 10% NaHCO₃ solution andextracted with EtOAc. The organic phase obtained is dried and solvent isevaporated. The title compound is obtained as the free amine compoundand converted to the hydrochloride salt by addition of 4M HCl solutionin dioxane. Solvent is evaporated and the residue obtained is stirredwith ether, the mixture obtained is filtered and the filtrate obtainedis dried to yield the title compound.

MS: 192 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.25

E) C-(7-Triethylsilanylethynyl-naphthalen-1-yl)-methylamine

A solution of 500 mg of C-(7-Chloro-naphthalen-1-yl)-methylaminehydrochloride, 5.4 mg of bis(acetonitrile)palladium (II) chloride, 29.8mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl and1.7 g of cesium carbonate in 7.5 ml of acetonitrile is stirred at rt for25 minutes. After adding 495 μl of (triethylsilyl)acetylene, the mixtureobtained is stirred at 90° for 2 hours, quenched with H₂O and extractedwith EtOAc. The organic phase obtained is washed with brine, dried andsolvent is evaporated. The residue obtained is purified by flashchromatography on silica gel (eluent: CH₂Cl₂/MeOH/NH₄OH 99/1/0.01 to95/5/0.01) the title compound is obtained.

MS: 279 [M-NH3+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 98/2/0.01)=0.22

F)(S)-1-[(7-Triethylsilanylethynyl-naphthalen-1-ylmethyl)-carbamoyl]-pyrrolidine-2-carboxylicacid

A 20% phosgene solution in 8 ml of toluene is added to 500 mg ofC-(7-triethylsilanylethynyl-naphthalen-1-yl)-methylamine and 479 μl ofdiisopropylethylamine in 40 ml of toluene. The solution obtained isstirred at reflux for 3 hours and another portion of a 20% phosgenesolution in 8 ml of toluene is added and stirred at reflux another hour.Solvent is evaporated. To the evaporation residue obtained 559 μl ofdiisopropylethylamine in 40 ml of THF and 213 mg of(S)-pyrrolidine-2-carboxylic acid are added. The mixture obtained isstirred for 1 hour and solvent is evaporated. The residue obtained ispurified by preparative HPLC (Waters Sun Fire C18 column, gradientwater/acetonitrile 95/5 to 0/100) to yield the title compound.

MS: 437 [M+H]+HPLC (method B): 4.366 minutes

G)(S)-1-[(7-Ethynyl-naphthalen-1-ylmethyl)-carbamoyl]-pyrrolidine-2-carboxylicacid

A solution of 250 mg of(S)-1-[(7-Triethylsilanylethynyl-naphthalen-1-ylmethyl)-carbamoyl]-pyrrolidine-2-carboxylicacid in 14 ml of THF is stirred at rt for 1 hour. Solvent is evaporatedand the residue obtained is purified by preparative HPLC (Waters SunFire C18 column, gradient water/acetonitrile 95/5 to 0/100) to yield thetitle compound.

MS: 323 [M+H]+ TLC, Rf (EtOAc/AcOH 50/1)=0.16

H) (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amidel24(2-pyridin-3-yl-ethyl)-amide]

11.6 mg of 3-(2-aminoethyl)pyridine, 4.05 μl of diisopropylethylamine,13.1 mg of 1-hydroxybenzotriazole and 18.8 mg ofN-(Ethyl-N′-(3-dimethylaminopropyl)carbothimide hydrochloride are addedto 20 mg of(S)-1-[(7-ethynyl-naphthalen-1-ylmethyl)-carbamoyl]-pyrrolidine-2-carboxylicacid in 1 ml of CH₂Cl₂. The reaction mixture obtained is stirred at rtfor 16 hours, solvent is evaporated and the residue obtained is purifiedby preparative HPLC (Waters Sun Fire C18 column, gradientwater/acetonitrile 95/5 to 0/100) to yield the title compound.

MS: 427 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.37.

Example 2 (S)-Pyrrolidine-1,2-dicarboxylic acid2-[(2-dimethylamino-ethyl)-amide]1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1using N,N-dimethylethylenediamine instead of 3-(2-aminoethyl)pyridine.

MS: 393 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.07

Example 3 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(2-pyridin-4-yl-ethyl)-amide]

The title compound is prepared analogously as described in example 1using 4-(2-aminoethyl)pyridine instead of 3-(2-aminoethyl)pyridine.

MS: 427 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.10

Example 4 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(6-methoxy-pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1using C-(6-Methoxy-pyridin-3-yl)-methylamine instead of3-(2-aminoethyl)pyridine.

MS: 443 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.275

Example 5 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(1-methyl-piperidin-4-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1using 1-(methylpiperidin-4-yl)methylamine instead of3-(2-aminoethyl)pyridine.

MS: 433 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.072

Example 6 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[4-(4-methyl-piperazin-1-yl)-benzylamide]

The title compound is prepared analogously as described in example 1using 4-(4-methylpiperazino)benzylamine instead of3-(2-aminoethyl)pyridine.

MS: 510 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.1

Example 7 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-(4-morpholin-4-ylmethyl-benzylamide)

The title compound is prepared analogously as described in example 1using 4-(morpholinomethyl)benzylamine instead of3-(2-aminoethyl)pyridine.

MS: 511 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 98/2/0.01)=0.26

Example 8 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide] 2-methylamide

The title compound is prepared analogously as described in example 1using methylamine hydrochloride instead of 3-(2-aminoethyl)pyridine.

MS: 336 [M+H]+ TLC, Rf (ethylacetate)=0.1

Example 9 (S)-Pyrrolidine-1,2-dicarboxylic acid2-{[2-(4-benzyl-piperazin-1-yl)-ethyl]-amide}1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1using 2-(4-Benzyl-piperazin-1-yl)-ethylamine instead of3-(2-aminoethyl)pyridine.

MS: 524 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.32

Example 10 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide] 2-[(2-methoxy-ethyl)-amide]

The title compound is prepared analogously as described in example 1using 2-methoxyethylamine instead of 3-(2-aminoethyl)pyridine.

MS: 380 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.276

Example 11 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1using 3-picolylamine instead of 3-(2-aminoethyl)pyridine.

MS: 413 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.17

Example 12 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-4-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1using 4-picolylamine instead of 3-(2-aminoethyl)pyridine.

MS: 413 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.215

Example 13 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-{[2-(4-methyl-piperazin-1-yl)-ethyl]-amide}

The title compound is prepared analogously as described in example 1using 1-(2-aminoethyl)-4-methylpiperazine instead of3-(2-aminoethyl)pyridine,

MS: 448 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.01)=0.088

Example 14 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(6-chloro-naphthalen-1-ylmethyl)-amide]2-{[2-(4-methoxy-phenyl)-ethyl]-amide} A)C-(6-Chloro-naphthalen-1-yl)-methylamine trifluoroacetic acid salt

The title compound is prepared analogously as described in example 1step C and D using (6-Chloro-naphthalen-1-yl)-methanol instead of(7-Chloro-naphthalen-1-yl)methanol.

MS: 175 [M-NH3+H]+ HPLC (method B): 1.935 min

B) (S)-2-[2-(4-Methoxy-phenyl)-ethylcarbamoyl]-pyrrolidine-1-carboxylicacid tert-butyl ester

18.9 g of N-(Ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochlorideare added to a cooled solution of 20.04 g of(S)-Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester, 14.9 g of4-methoxyphenethylamine, 16.9 ml of diisopropylethylamine and 13.2 g of1-hydroxy-benzotriazole in 250 ml of CH₂Cl₂. The reaction mixtureobtained is stirred at rt for 16 hours, the reaction is quenched withaq. 2N HCl solution and the aq. phase obtained is extracted with CH₂Cl₂.The combined organic phases obtained are washed with aq. 2N HClsolution, brine and aq. saturated NaHCO₃ solution, dried and solvent isevaporated. The residue obtained is purified by recrystallisation withEtOAc/hexane (1/3) to afford the title compound.

MS: 349 [M+H]+ TLC, Rf (ethylacetate/hexane 1/1)=0.21

C) (S)-Pyrrolidine-2-carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-amide

4N HCl solution in 41 ml of dioxane is added to a fine suspension of16.78 g of(S)-2-[2-(4-Methoxy-phenyl)-ethylcarbamoyl]-pyrrolidine-1-carboxylicacid tert-butyl ester in 40 ml of dioxane. After stirring under poorcooling with an ice-bath for 2.5 hours, solvent is evaporated, theresidue obtained is cooled over night at 0° and resulting crystals arestirred with 150 ml of tert-butylmethylether, filtered and dried toyield the title compound.

MS: 249 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.35

D) (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(16-chloro-naphthalen-1-ylmethyl)-amide]2-{[4-methoxy-phenyl)-ethyl]-amide}

A solution of 33 mg of C-(6-Chloro-naphthalen-1-yl)-methylaminetrifluoroacetic acid salt, 22 mg of 4-nitrophenylchloroformate and 25 μlof pyridine in 3 ml of CH₂Cl₂ is stirring at rt for 1 hour. 30 mg of(S)-Pyrrolidine-2-carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-amide and37 μl of diisopropylethylamine are added. The reaction mixture obtainedis stirred at rt for 16 hours, solvent is evaporated and the residueobtained is purified by preparative HPLC (Waters Sun Fire C18 column,gradient water/acetonitrile 95/5 to 0/100) to yield the title compound.

MS: 466 [M+H]+ TLC, Rf (EtOAc)=0.363

Example 15 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-chloro-naphthalen-1-ylmethyl)-amide]2-{[2(4-methoxy-phenyl)-ethyl]-amide}

The title compound is prepared analogously as described in example 14using C-(7-Chloro-naphthalen-1-yl)-methylamine trifluoroacetic acid saltinstead of C-(6-Chloro-naphthalen-1-yl)-methylamine trifluoroacetic acidsalt.

MS: 466 [M+H]+ TLC, Rf (EtOAc)=0.45

Example 16 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(5-bromo-benzo[b]thiophen-3-ylmethyl)-amide]2-{[2-(4-methoxy-phenyl)-ethyl]-amide}

The title compound is prepared analogously as described in example 14using C-(5-Bromo-benzo[b]thiophen-3-yl)-methylamine instead ofC-(6-Chloro-naphthalen-1-yl)-methylamine trifluoroacetic acid salt.

MS: 518 [M+H]+ TLC, Rf (EtOAc/cyclohexyane 2/1)=0.1

Example 17 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(5-chloro-benzo[b]thiophen-3-ylmethyl)-amide]2-{[2-(4-methoxy-phenyl)-ethyl]-amide}

The title compound is prepared analogously as described in example 14using C-(5-chloro-benzo[b]thiophen-3-yl)-methylamine hydrochlorideinstead of C-(6-Chloro-naphthalen-1-yl)-methylamine trifluoroacetic acidsalt.

MS: 472 [M+H]+ TLC, Rf (EtOAc/cyclohexyane 2/1)=0.209

Example 18 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-{[2-(4-methoxy-phenyl)-ethyl]-amide} A)(S)-Pyrrolidine-1,2-dicarboxylic acid2-{[2-(4-methoxy-phenyl)-ethyl]-amide}1-[(7-triethylsilanylethynyl-naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 14using C-(7-Triethylsilanylethynyl-naphthalen-1-yl)-methylamine insteadof C-(6-Chloro-naphthalen-1-yl)-methylamine trifluoroacetic acid salt.

MS: 570 [M+H]+

B) (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-{[2-(4-methoxy-phenyl)-ethyl]-amide}

The title compound is prepared analogously as described in example 1part G using (S)-Pyrrolidine-1,2-dicarboxylic acid2-{[2-(4-methoxy-phenyl)-ethyl]-amide}1-[(7-triethylsilanylethynyl-naphthalen-1-ylmethyl)-amide] instead of(S)-1-[(7-Triethylsilanylethynyl-naphthalen-1-ylmethyl)-carbamoyl]-pyrrolidine-2-carboxylicacid.

MS: 456 [M+H]+ TLC, Rf (EtOAc/cyclohexane 2/1)=0.15

Example 19 (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide] A)(2S,4R)-4-Methoxy-2-[(pyridin-3-ylmethyl)-carbamoyl]-pyrrolidine-1-carboxylicacid tert-butyl ester

The title compound is prepared analogously as described in example 14step B using (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid1-tert-butyl ester instead of (S)-Pyrrolidine-1,2-dicarboxylic acid1-tert-butyl ester and 3-picolylamine instead of4-methoxyphenethylamine.

MS: 336 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 9019/1)=0.36

B) ((2S,4R)-4-Methoxy-pyrrolidine-2-carboxylic acid(pyridin-3-ylmethyl)-amide

The title compound is prepared analogously as described in example 14step C using(2S,4R)-4-Methoxy-2-[(pyridin-3-ylmethyl)-carbamoyl]-pyrrolidine-1-carboxylicacid tert-butyl ester instead of(S)-2-[2-(4-Methoxy-phenyl)-ethylcarbamoyl]-pyrrolidine-1-carboxylicacid tert-butyl ester.

MS: 236 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.31

C) (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid2-[(pyridin-3-ylmethyl)-amide]1-[(7-triethylsilanylethynyl-naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1part F using ((2S,4R)-4-Methoxy-pyrrolidine-2-carboxylic acid(pyridin-3-ylmethyl)-amide instead of (S)-pyrrolidine-2-carboxylic acid.

MS: 557 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.44

D) (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 18part B using (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid2-[(pyridin-3-ylmethyl)-amide]1-[(7-triethylsilanylethynyl-naphthalen-1-ylmethyl)-amide] instead of(S)-Pyrrolidine-1,2-dicarboxylic acid2-{[2-(4-methoxy-phenyl)-ethyl]-amide}1-[(7-triethylsilanylethynyl-naphthalen-1-ylmethyl)-amide].

MS: 443 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.23

Example 20 (S)-Piperidine-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 19using (S)-Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester instead of(2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester.

MS: 427 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.36

Example 21 (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid2-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]1-[(pyridin-3-ylmethyl)-amide] A)(S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid 2-tert-butylester 1-ethyl ester

2.36 g of Di(tert-butyl)dicarbonate are added in 3-times to a mixture of1.65 g of (S)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid ethylester and 1.45 g of NaCO₃ in 20 ml of dioxane and 10 ml of H₂O. Thereaction mixture obtained is stirred at rt for 4 hours, the reaction isquenched with brine and the residue obtained is extracted with EtOAc.The organic phase obtained is washed with brine, dried and solvent isevaporated before purification by flash chromatography on silica gel iscarried out (eluent: cyclohexane/EtOAc 9/1) to yield the title compound.

MS: 228 [M-isobutene+H]+ TLC, Rf (cyclohexane/EtOAc 4/1)=0.353

B) (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid 2-tert-butylester

A mixture of 2 g of (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylicacid 2-tert-butyl ester 1-ethyl ester and 449 mg of LiOH in 30 ml of THFand 10 ml of H₂O is stirred at rt for 16 hours. The reaction is quenchedwith brine, acidified to pH 2 with aq. 2N HCl solution and extractedwith EtOAc. The combined organic phases obtained are washed with brine,dried and solvent is evaporated to afford the title compound.

MS: 200 [M+H]+ TLC, Rf (hexane/EtOAc/AcOH 3/6/1)=0.71

C)(S)-1-[(Pyridin-3-ylmethyl)-carbamoyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylicacid tert-butyl ester

50% propylphosphonic anhydride solution in 650 μl of DMF is added to asolution of 200 mg of(S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid 2-tert-butylester, 7.42 mg of 4-dimethylaminopyridine and 650 μl ofdiisopropylethylamine in CH₂Cl₂. After stirring at rt for 16 hours, thereaction is quenched with aq. 2N NaOH solution, eluted through a ChemElut extraction with CH₂Cl₂ and solvent is evaporated beforepurification by preparative HPLC is carried out (Waters Sun Fire C18column, gradient water/acetonitrile 95/5 to 0/100) to yield the titlecompound.

MS: 346 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.42

D) (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid2-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]1-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 19using(S)-1-[(Pyridin-3-ylmethyl)-carbamoyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylicacid tert-butyl ester instead of(2S,4R)-4-Methoxy-2-[(pyridin-3-ylmethyl)-carbamoyl]-pyrrolidine-1-carboxylicacid tert-butyl ester.

MS: 453 [M+H] TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.29

Example 22 (S)-2,3-Dihydro-indole-1,2-dicarboxylic acid1-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 21using (S)-2,3-Dihydro-indole-1,2-dicarboxylic acid 1-tert-butyl esterinstead of (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid2-tert-butyl ester.

MS: 461 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.42

Example 23 (S)-1,3-Dihydro-isoindole-1,2-dicarboxylic acid2-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]1-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 21using 1,3-Dihydro-isoindole-1,2-dicarboxylic acid 2-tert-butyl esterinstead of (S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid2-tert-butyl ester.

MS: 461 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.34

Example 24 (1R,2S,5S)-3-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid3-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 21using (1R,2S,5S)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid3-tert-butyl ester instead of(S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid 2-tert-butylester.

MS: 425 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.32

Example 25 (1S,2S,5R)-3-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid3-[(7-ethynyl-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 21using (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid3-tert-butyl ester instead of(S)-Hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid 2-tert-butylester.

MS: 425 [M+H]+ TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 90/9/1)=0.36

Example 26 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide) A)(4-Polystyryloxy-2,6-dimethoxy-benzyl)-phenethyl-amine

25 g of commercially available2-(3,5-dimethoxy-4-formylphenoxy)ethoxymethyl polystyrene is washed 4times with a 10/3 mixture of DCE and TMOF (150 ml). The resin obtainedis suspended in the above 10/3 mixture of DCE and TMOF (150 ml) againand treated with 15.1 g of phenethylamine. The slurry obtained is shakenon an orbital shaker at it for 16 hours, the resin obtained is drainedand washed successively with DMA, THF and CH₂Cl₂. A preformed solutionof 5.1 ml of MeOH, 7.2 ml of AcOH and 125 mmol borane-pyridine complexin CH₂Cl₂ is added to the resin and shaking is resumed for 4 hours atrt. The resin obtained is drained and washed successively with DMA,AcOH/DMA (1/19), DMA, THF/H₂O (9/1), THF, CH₂Cl₂, MeOH, THF, MeOH. Thetitle compound is thoroughly dried under vacuum to constant weight.

B)(6)-2-[(4-Polystyryloxy-2,6-dimethoxy-benzyl)-phenethyl-carbamoyl]-pyrrolidine-1-carboxylicacid 9H-fluoren-9-ylmethyl ester

122 mg of (S)-pyrrolidine-1,2-dicarboxylic acid1-(9H-fluoren-9-ylmethyl) ester followed by 126 μl of DIPEA are added toa solution of 140 mg of HATU in 1.20 ml of NMP. The solution obtained isadded onto 200 mg of the(4-polystyryloxy-2,6-dimethoxy-benzyl)-phenethyl-amine resin (loadingapproximated as 0.6 mmol/g, 0.12 mmol) and the slurry obtained is shakenfor 2 hours at 60°. The resin obtained is washed successively with DMA,MeOH, CH₂Cl₂, and treated for one hour at rt with a 1M solution of Ac₂Oand 2M DIPEA in 5 ml of CH₂Cl₂. The resin obtained is drained and washed3 consecutive times using the above solvent sequence of DMA, MeOH andCH₂Cl₂.

C) (S)-Pyrrolidine-2-carboxylic acid(4-polystyryloxy-2,6-dimethoxy-benzyl)-phenethyl-amide

The resin(S)-2-[(4-Polystyryloxy-2,6-dimethoxy-benzyl)-phenethyl-carbamoyl]-pyrrolidine-1-carboxylicacid 9H-fluoren-9-ylmethyl ester obtained in step B (0.12 mmol of boundspecies) is suspended in a mixture of piperidine and DMA (1/4, 3 ml) andshaken on an orbital shaker for 20 minutes before draining and washingsuccessively with DMA, MeOH, and CH₂Cl₂. The resin obtained is submittedone additional time to the piperidine and DMA solution for 20 minutesbefore final washing with DMA, MeOH, and CH₂Cl₂ to give the titlecompound.

D) (S)-Pyrrolidine-1,2-dicarboxylic acid2-[(4-polystyryloxy-2,6-dimethoxy-benzyl)-phenethyl-amide]1-[(naphthalen-1-ylmethyl)-amide]

210 mg of 1-(aminomethyl)naphthalene followed by 210 μl of DIPEA arecautially added to a solution of 249 mg of 4-nitrophenylchloroformate in2.60 ml of DCE. The solution obtained is stirred for 2.5 hours at rt andadded to the resin (0.12 mmol of bound species) obtained in step C. Theslurry of resin obtained is shaken at it for 17 hours on an orbitalshaker. The resin obtained is drained and washed 3 consecutive timesusing a sequence of DMA, MeOH and CH₂Cl₂ to give the title compound.

E) (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(naphthalen-1-ylmethyl)-amide] 2-(Phenethyl-amide)

The resin of step D) (0.12 mmol of bound species) is treated with asolution of 20% TFA in 2 ml of CH₂Cl₂ for 1 hour at rt. The resinobtained is filtered and washed 3 times with 2 ml of CH₂Cl₂. Thecombined filtrates obtained are concentrated and the residue obtained isdissolved in MeOH and submitted to purification by preparative HPLC togive the title compound.

MS: 402 [M+H]+, 424 [M+Na]+ HPLC: 4.44 min, 100% UV purity

Example 27 (2S,4S)-4-Phenyl-pyrrolidine-1,2-dicarboxylic acid1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide)

The title compound is prepared analogously as described in example 26using (2S,4S)-4-phenyl-pyrrolidine-1,2-dicarboxylic acid1-(9H-fluoren-9-ylmethyl) ester instead of(S)-pyrrolidine-1,2-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester instep B.

MS: 478 [M+H]+, 500 [M+Na]+ HPLC: 5.22 minutes

Example 28 (2S,4R)-4-Phenyl-pyrrolidine-1,2-dicarboxylic acid1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide)

The title compound is prepared analogously as described in example 26using (2S,4R)-4-phenyl-pyrrolidine-1,2-dicarboxylic acid1-(9H-fluoren-9-ylmethyl) ester instead of(S)-pyrrolidine-1,2-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester instep B.

MS: 478 [M+H]+, 500 [M+Na]+ HPLC: 5.13 minutes

Example 29 (S)-3,4-Dihydro-1H-isoquinoline-2,3-dicarboxylic acid2-[(naphthalen-1-ylmethyl)-amide] 3-(phenethyl-amide)

The title compound is prepared analogously as described in example 26using (S)-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid2-(9H-fluoren-9-ylmethyl) ester instead of(S)-pyrrolidine-1,2-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester instep B.

MS: 464 [M+H]+, 486 [M+Na]+ HPLC: 5.04 minutes

Example 30 (S)-Piperidine-1,2-dicarboxylic acid1-[(naphthalen-1-ylmethyl)-amide] 2-(phenethyl-amide)

The title compound is prepared analogously as described in example 26using (S)-piperidine-1,2-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl)ester instead of (S)-pyrrolidine-1,2-dicarboxylic acid1-(9H-fluoren-9-ylmethyl) ester in step B.

MS: 438 [M+Na]+ HPLC: 4.77 minutes

Example 31 (S)-Pyrrolidine-1,2-dicarboxylic acid2-{[2-(4-methoxy-phenyl)-ethyl]-amide} 1-[(naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 26using 2-(4-Methoxy-phenyl)-ethylamine instead of phenethylamine in stepA.

MS: 432 [M+H]+, 454 [M+Na]+ HPLC: 4.23 minutes

Example 32 (S)-Pyrrolidine-1,2-dicarboxylic acid 2-benzylamide1-[(naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 26using benzylamine instead of phenethylamine in step A.

MS: 388 [M+H]+, 410 [M+Na]+HPLC: 4.11 minutes

Example 33 (S)-Pyrrolidine-1,2-dicarboxylic acid2-cyclohexylmethyl-amide 1-[(naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 26using C-cyclohexyl-methylamine instead of phenethylamine in step A.

MS: 394 [M+H]+, 416 [M+Na]+HPLC: 4.68 minutes

Example 34 (S)-Pyrrolidine-1,2-dicarboxylic acid2-[(3-methyl-butyl)-amide] 1-[(naphthalen-1-ylmethyl)-amide]

The title compound is prepared analogously as described in example 26using 3-methyl-butylamine instead of phenethylamine in step A.

MS: 368 [M+H]+, 390 [M+Na]+ HPLC: 4.34 minutes

Example 35 (S)-Pyrrolidine-1,2-dicarboxylic acid1-[(naphthalen-1-ylmethyl)-amide]2-[(tetrahydro-furan-2-ylmethyl)-amide]

The title compound is prepared analogously as described in example 26using C-(tetrahydro-furan-2-yl)-methylamine instead of phenethylamine instep A.

MS: 382 [M+H]+, 404 [M+Na]+ HPLC: 3.47 minutes

Example 36 (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid3-[(7-chloro-naphthalen-1-ylmethyl)-amide]2-[(pyridin-3-ylmethyl)-amide]

The title compound is prepared analogously as described in example 1step F using (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid(pyridin-3-ylmethyl)-amide instead of (S)-pyrrolidine-2-carboxylic acidand C-(7-chloro-naphthalen-1-yl)-methylamine instead ofC-(7-triethylsilanyleethynylnaphthalen-1-yl)-methylamine. The titlecompound is dissolved in CH₂Cl₂ and treated with polymer boundbenzylamine.

MS: 434.9 [M+H]+, 432.8 [M−H]− TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.5) 0.10

Example 37 (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid3-[(7-chloro-naphthalen-1-ylmethyl)-amide]2-{[2-(4-methoxy-phenyl)-ethyl]-amide}

The title compound is prepared analogously as described in example 1step F using (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid[2-(4-methoxy-phenyl)-ethyl]-amide instead of(S)-pyrrolidine-2-carboxylic acid andC-(7-chloro-naphthalen-1-yl)-methylamine instead ofC-(7-triethylsilanyleethynylnaphthalen-1-yl)-methylamine. The titlecompound is dissolved in CH₂Cl₂ and treated with polymer boundbenzylamine.

MS: 477.9 [M+H]+, 475.8 [M−H]− TLC, Rf (CH₂Cl₂/MeOH/NH₄OH 95/5/0.5) 0.40

TABLE 1 A compound of formula

Example No. R₂  1

 2

 3

 4

 5

 6

 7

 8 —CH₃  9

10

11

12

13

18

TABLE 2 A compound of formula

Example No. Y 19

20

21

22

23

24

25

TABLE 3 A compound of formula

Example No. Y 26

27

28

29

30

31

32

33

34

35

Example No. 14

Example No. 15

Example No. 16

Example No. 17

Example No. 36

Example No. 37

Example 38 A) Test on Recovery of Skin Barrier Disruption in Mice

Method:

Skin barrier disruption is achieved in groups of hairless SKH1 mice withrepeated stripping of the skin with S-Sqame® skin sampling disks. Theprocedure is completed when transepidermal water loss (TEWL) achieved≧40mg/cm²/h. TEWL is assessed with a Tewameter TM210 (Courage Khazaka,Cologne, Del.). Immediately after barrier disruption 30 μl of thecompound of example 37(=Test compound 1) is applied at 10 mMconcentration. Controls animals are treated similarly with the solvent(EtOH/propylene glycol, 3/7 (v/v)) alone. TEWL is measured before,immediately after, and at 3 hrs after barrier disruption. In eachanimal, the percentage recovery is calculated using the formula:(1−[TEWL at 3 hrs−base line TEWL]/[TEWL immediately after stripping−baseline TEWL])×100%. Table 1 shows that a single application of the Testcompound 1 accelerates barrier repair by 65-76% compared to repair inmice treated with the solvent alone (p<0.001).

TABLE 1 % Recovery in barrier disruption Mean (SD values), Animals n: 8or 12 animals per group) Treated with Test compound 1 at 10 mM 76(3.3)*** Treated with solvent alone 56 (7.1) **p < 0.001 vs solventcontrol

B) Test on Anti-Inflammatory Activity in Murine Model of IrritantContact Dermatitis (ICD)

Method:

Crl:NMRI mice are challenged with 10 μl 0.005% phorbol12-myristat-13-acetate (TPA) on the inner surface of the right ear. Theunchallenged left ears serve as normal controls and dermatitis isevaluated from the difference in auricular weight (taken as a measure ofinflammatory swelling) 6 hours after the challenge. The animals aretreated topically with 10 μl of the test compound 1 or the solvent 30minutes prior to the challenge. The efficacy of the treatment iscalculated as the percentage inhibition of inflammatory auricularswelling relative to animals treated with the vehicle alone.

Table 2 shows that TPA-induced irritant dermatitis isconcentration-dependently inhibited. The inflammatory swelling isinhibited by 54-73% at 20 mM concentrations; no statisticallysignificant inhibition was observed at 3 mM.

TABLE 2 % Inhibition inflammatory swelling [Mean ± SEMvalues^((n animals))) Concentration Test compound 1 30 mM 73 ± 7.0***²⁴10 mM 41 ± 5.3***²⁴  3 mM 13 ± 6.1^(ns24) ***p < 0.001, **p < 0.01 vscontrols, ^(ns)not statistically significant (p > 0.05)

C) Test on Anti-Inflammatory Activity in Swine Model of Allergic ContactDermatitis (ACD)

Eight days before the elicitation of the ACD, 500 μl of 10%2,4-dinitrofluorobenzene (DNFB, dissolved in DMSO/acetone/olive oil[1/5/3, v/v/v]) are applied epicutaneously in divided volumes onto thebasis of both ears and onto both groins (100 μl/site) for sensitization.The challenge reactions are elicited with 15 μl of DNFB (1.0%) oncontralateral test sites (each 7 cm² in size) of the shaved dorsolateralback. For treatment, the compound of example 11 (=Test compound 2) andthe placebo (solvent only) are applied contralaterally to 2 test sitesin each animal 0.5 and 6 hours after the challenge. The test sites areclinically examined 24 hours after the challenge when inflammationpeakes. The changes are scored on a scale from 0 to 4 (Table XY),allowing a combined maximal score of 12 per designated site. Skinreddening is measured reflectometrically using a* values (see Table 3)

TABLE 3 Scoring of clinical signs of test sites affected with ACD ScoreErythema/Intensity Erythema/Extent Induration 0 absent absent absent 1scarcely visible small spotted scarcely palpable 2 mild large spottedmild hardening 3 pronounced confluent pronounced hardening 4 severehomogenous pronounced and elevated (or livid discoloring) rednesshardening

Table 4 summarizes the results of the treatment of test sites affectedwith ACD: A 1% solution of the Test compound 2 inhibits clinicalinflammatory changes by 42% (p<0.01) and measured skin redness by 32(p<0.05)

TABLE 4 Clinical score A* value Test sites (Mean, SD, n: 8+) (Mean, SD,n: 8+) Treated with 1%  4.1 (1.3)  7.7 (1.6) Test compound 2 Treatedwith placebo  7.1 (1.8) 11.7 (2.3) (solvent) Inhibition vs placebo- 42.4(11.1) 31.9 (18.4) treated sites +2 test sites each in 4 animals

REFERENCES

-   1 Skytt A., Stromqvist M. and Egelrud T. (1995) Primary substrate    specificity of recombinant human stratum corneum chymotryptic    enzyme. Biochem Biophys Res Commun 211, 586-589.-   2 Egelrud T. (1993) Purification and preliminary characterization of    stratum corneum chymotryptic enzyme: a proteinase that may be    involved in desquamation. J. Invest. Dermatol. 101, 200-204.-   3 Yousef G. M., Scorilas A., Magklara A., Soosaipillai A. and    Diamandis E. P. (2000) The KLK7 (PRSS6) gene, encoding for the    stratum corneum chymotryptic enzyme is a new member of the human    kallikrein gene family—genomic characterization, mapping, tissue    expression and hormonal regulation. Gene 254, 119-128.-   4 Simon M., Jonca N., Guerrin M., Haftek M., Bernard D., Caubet C.,    Egelrud T., Schmidt R. and Serre G. (2001) Refined characterization    of corneodesmosin proteolysis during terminal differentiation of    human epidermis and its relationship to desquamation. J. Biol. Chem.    276(23), 20292-20299.-   5 Caubet C., Jonca N., Brattsand M., Guerrin M., Bernard D., Schmidt    R., Egelrud T., Simon M. and Serre G. (2004) Degradation of    corneodesmosome proteins by two serine proteases of the kallikrein    family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J. Invest. Dermatol. 122,    1235-1244.-   6 Brattsand M., Stefansson K., Lundh C., Haasum Y. and    Egelrud T. (2005) A proteolytic cascade of kallikreins in the    stratum corneum. J. Invest. Dermatol. 124(1), 198-203.-   7 Hachem J. P., Man M. Q., Crumrine D., Uchida Y., Brown B. E.,    Rogiers V., Roseeuw D., Feingold K. R. and Elias P. M. (2005)    Sustained serine proteases activity by prolonged increase in pH    leads to degradation of lipid processing enzymes and profound    alterations of barrier function and stratum corneum integrity. J.    Invest. Dermatol. 125(3), 510-520.-   8 Nylander-Lundqvist E. and Egelrud T. (1997) Formation of active    IL-1β from pro-IL-1β catalyzed by stratum corneum chymotryptic    enzyme in vitro. Acta Derm. Venereol. 77(3), 203-206.-   9 Vasilopoulos Y., Cork M. J., Murphy R., Williams H. C.,    Robinson D. A., Duff G. W., Ward S. J. and Tazi-Ahnini R. (2004)    Genetic association between an AACC insertion in the 3′UTR of the    stratum corneum chymotryptic enzyme gene and atopic dermatitis. J.    Invest. Dermatol. 123, 62-66.-   10 Schechter N. M., Choi E. J., Wang Z. M., Hanakawa Y., Stanley J.    R., Kang Y., Clayman G. L. and Jayakumar A. (2005) Inhibition of    human kallikreins 5 and 7 by the serine protease inhibitor    lympho-epithelial Kazal-type inhibitor (LEKTI). Biol. Chem. 386,    1173-1184.-   11 Franzke C. W., Baici A., Bartels J., Christophers E. and    Wiedow O. (1996) Antileukoprotease inhibits stratum corneum    chymotryptic enzyme—Evidence for a regulative function in    desquamation. J. Biol. Chem. 271, 21886-21890.-   12 Descargues P., Deraison C., Bonnart C., Kreft M., Kishibe M.,    Ishida-Yamamoto A., Elias P., Barrandon Y., Zambruno G.,    Sonnenberg A. and Hovnanian A. (2005) Spink5-deficient mice mimic    Netherton syndrome through degradation of desmoglein 1 by epidermal    protease hyperactivity. Nat. Genet. 37(1), 56-65.-   13 Walley A. J., Chavanas S., Moffatt M. F., Esnouf R. M., Ubhi B.,    Lawrence R., Wong K., Abecasis G. R., Jones E. Y., Harper J. I.,    Hovnanian A. and Cookson W. O. (2001) Gene polymorphism in Netherton    and common atopic disease. Nat. Genet. 29(2), 175-178.-   14 Nishio Y., Noguchi E., Shibasaki M., Kamioka M., Ichikawa E.,    Ichikawa K., Umebayashi Y., Otsuka F. and Arinami T. (2003)    Association between polymorphisms in the SPINK5 gene and atopic    dermatitis in the Japanese. Genes Immun. 4(7), 515-517.-   15 Descargues P., Deraison C., Prost C., Fraitag S.,    Mazereeuw-Hautier J., D'Alessio M., Ishida-Yamamoto A., Bodemer C.,    Zambruno G. and Hovnanian A. (2006) Corneodesmosomal cadherins are    preferential targets of stratum corneum trypsin- and    chymotrypsin-like hyperactivity in Netherton syndrome. J. Invest.    Dermatol. 126(7), 1622-1632.-   16 Hachem J. P., Wagberg F., Schmuth M., Crumrine D., Lissens W.,    Jayakumar A., Houben E., Mauro T. M., Leonardsson G., Brattsand M.,    Egelrud T., Roseeuw D., Clayman G. L., Feingold K. R., Williams M.    L., Elias P. M. (2006) Serine protease activity and residual LEKTI    expression determine phenotype in Netherton syndrome. J. Invest.    Dermatol. 126(7), 1609-1621.-   17 Hansson L., Baeckman A., Ny A., Edlund M., Ekholm E.,    Hammarstroem B. E., Toernell J., Wallbrandt P., Wennbo H., and    Egelrud T. (2002) Epidermal Overexpression of Stratum Corneum    Chymotryptic Enzyme in Mice: A Model for Chronic Itchy    Dermatitis, J. Invest. Dermatol. 118, 444-449.-   18 Ny A. and Egelrud T. (2003) Transgenic mice over-expressing a    serine protease in the skin: evidence of interferon    gamma-independent MHC II expression by epidermal keratinocytes. Acta    Derm. Venereol. 83, 322-327.-   19 Ny A. and Egelrud T. (2004) Epidermal hyperproliferation and    decreased skin barrier function in mice overexpressing stratum    corneum chymotryptic enzyme. Acta Derm. Venereol. 84, 18-22.-   20 Ekholm E. and Egelrud T. (1999) Stratum corneum chymotryptic    enzyme in psoriasis. Arch. Dermatol. Res. 291(4), 195-200.-   21 Otwinowski, Z. and Minor, W. (1997) Processing of X-ray    diffraction data collected in oscillation mode. Methods in    Enzymology, 276, C. W. Carter, Jr. and R. M. Sweet, Eds., Academic    Press.-   22 Kabsch W. (1993) Automatic Processing of Rotation Diffraction    Data from Crystals of Initially Unknown Symmetry and Cell    Constants. J. App. Cryst. 26, 795-800.-   23 Kroemer M., Dreyer M. K. and Wendt K. U. (2004) APRV—a program    for automated data processing, refinement and visualization. Acta    Cryst. D60, 1679-82.-   24 Vagin A., and Teplyakov A. (1997) MOLREP: an automated program    for molecular replacement. J. Appl. Cryst. 30, 1022-1025.-   25 Laxmikanthan G., Blaber S. I., Bernett M. J., Scarisbrick I. A.,    Juliano M. A. and Blaber M. (2005) 1.70 Å X-ray structure of human    apo kallikrein 1: structural changes upon peptide    inhibitor/substrate binding. Proteins 58(4), 802-814.-   26 Brünger A. T., Adams P. D., Clore G. M., DeLano W. L., Gros P.,    Grosse-Kunstleve R. W., Jiang J.-S., Kuszewski J., Nigles M.,    Pannu N. S., Read R. J., Rice L. M., Simonson T. and    Warren G. L. (1998) Crystallography & NMR System: A new software    suite for macromolecular structure determination. Acta Cryst., D54,    905-921.-   27 Johns T. A., Zou J. Y., Cowan S. W. and Kjeldgaard M. (1991)    Improved methods for building protein models in electron density    maps and the location of errors in these models. Acta Cryst., A47,    110-119.-   28 Engh R. A. and Huber R. (1991) Accurate bond and angle parameters    for X-ray protein structure refinement. Acta Cryst. A47, 392-400.-   29 Laskowski R. A., MacArthur M. W., Moss D. S, and    Thornton J. M. (1993) PROCHECK: a program to check the    stereochemical quality of protein structures. J. Appl. Cryst. 26,    238-291-   30 Birktoft J. J., Kraut J. and Freer S. T. (1976) A detailed    structural comparison between the charge relay system in    chymotrypsinogen and in alpha-chymotrypsin. Biochemistry 15(20),    4481-5.-   31 Bernett M. J., Blaber S. I., Scarisbrick I. A., Dhanarajan P.,    Thompson S. M. and Blaber M. (2002) Crystal structure and    biochemical characterization of human kallikrein 6 reveals that a    trypsin-like kallikrein is expressed in the central nervous    system. J. Biol. Chem. 277(27), 24562-24570.-   32 Kishi T., Kato M., Shimizu T., Kato K., Matsumoto K., Yoshida S.,    Shiosaka S., Hakoshima T. (1999) Crystal structure of neuropsin, a    hippocampal protease involved in kindling epileptogenesis. J. Biol.    Chem. 274, 4220-4224.-   33 Debela M., Magdolen V., Schechter N., Valachova M., Lottspeich    F., Craik C. S., Choe Y., Bode W. and Goettig P. (2006) Specificity    profiling of seven human tissue kallikreins reveals individual    subsite preferences. J. Biol. Chem. E-PUB.-   34 Yamasaki K., Schauber J., Coda A., Lin H., Dorschner R. A.,    Schechter N. M., Bonnart C., Descargues P., Hovnanian A. and    Gallo R. L. (2006) Kallikrein-mediated proteolysis regulates the    antimicrobial effects of cathelicidins in skin. FASEB J. 2006    October; 20(12):2068-80.

1. A crystal of human kallikrein 7 comprising the binding pocket havinga three-dimensional structure characterized by the structure coordinatesof Table
 3. 2. The crystal of claim 1 further comprising aco-crystallised ligand.
 3. A computer readable medium comprising datastorage material encoded with computer readable data wherein said datacomprises the structure coordinates of a crystal according to claim 1.4. Use of a crystal according to any one of claim 1 or 2, for thegeneration of crystal structure data.
 5. A method of identifying aligand that binds to kallikrein 7 comprising the steps of: (i)generating a three dimensional structure data using the crystalstructure data of claim 1 to select and/or design a potential ligandthat binds to kallikrein 7, and (ii) identifying among the potentialligand selected in step (i), those ligands that bind to kallikrein 7 inan in vitro, in vivo or cell-based assay.
 6. A modulator of kallikrein 7characterised in that it binds in the binding pocket having athree-dimensional structure characterized by the structure coordinatesof Table
 3. 7. A modulator of kallikrein 7 as defined in claim 6characterised in that it is a compound of formula

Or a salt thereof wherein R₁ is hydrogen, cyano, (C₁₋₈)alkyl,(C₂₋₈)alkenyl, (C₂₋₈)alkynyl, halogen, (C₁₋₈)alkylamino,(C₁₋₈)alkylamino(C₁₋₈)alkyl, (C₁₋₈)alkoxy, halo(C₁₋₈)alkyl, X is CH═CH,NH, N═CH, O or S, Y is a group of formula

wherein the N-containing ring system is optionally annelated with(C₃₋₈)cycloalkyl, (C₈₋₁₈)aryl or heterocyclyl having 5 to 6 ring membersand 1 to 4 heteroatoms selected from N, O, S, n is 1, 2 or 3, R₂ is(C₁₋₈)alkyl, (C₁₋₈)alkylamino, (C₁₋₈)alkylamino(C₁₋₈)alkyl,di(C₁₋₈)alkylamino(C₁₋₈)alkyl, halo(C₁₋₈)alkyl, (C₁₋₈)alkoxy,(C₁₋₈)alkoxy(C₁₋₈)alkyl, or (CH₂)_(m)-Z, wherein Z is unsubstituted orsubstituted (C₃₋₈)cycloalkyl, (C₈₋₁₈)aryl or heterocyclyl having 5 to 6ring members and 1 to 4 heteroatoms selected from N, O, Si; and m is 0,1 or 2, R₃ is hydrogen, (C₁₋₈)alkyl, (C₁₋₈)alkoxy, (C₈₋₁₈)aryl orheterocyclyl having 5 to 6 ring members and 1 to 4 heteroatoms selectedfrom N, O, S.
 8. A compound according to claim 7, wherein R₁ ishydrogen, ethynyl, chloro or bromo, X is CH═CH or S, Y is a group offormula (II), wherein the N-containing ring system is optionallyannelated with cyclopropyl, cyclopentyl or phenyl, n is 1 or 2, R₂ is(C₁₋₈)alkyl, (C₁₋₄alkylamino, di(C₁₋₄)alkylamino(C₁₋₄)alkyl,(C₁₋₄)alkoxy, (C₁₋₄)alkoxy(C₁₋₄)alkyl or a group (CH₂)_(m)-Z, wherein Zis unsubstituted cyclohexyl, unsubstituted phenyl, phenyl substituted by(C₁₋₄)alkoxy, phenyl substituted by heterocyclyl having 6 ring membersand 1 or 2 heteroatoms selected from N, O, or unsubstituted orsubstituted heterocyclyl having 6 ring members and 1 or 2 heteroatomsselected from N, 0; m is 1 or 2, R₃ is hydrogen or (C₁₋₄)alkoxy.
 9. Acompound of claim 7, wherein Y is a group of formula (II), wherein theN-containing ring system is optionally annelated with cyclopropyl,cyclopentyl or phenyl, R₂ is methyl, dimethylaminoethyl, methoxyethyl,or a group (CH₂)_(m)-Z, wherein Z is unsubstituted cyclohexyl,unsubstituted phenyl, phenyl substituted by methoxy, piperazinyl ormorpholinyl; pyridinyl, piperidinyl, tetrahydrofuranyl, unsubstitutedpiperazinyl or piperazinyl substituted by methyl or phenyl, and m, n,R₁, R₃ and X are as defined above.
 10. A compound of claim 7 in the formof a salt.
 11. A compound of claim 7 for use as a pharmaceutical.
 12. Apharmaceutical composition comprising a compound of claim 7 inassociation with at least one pharmaceutical excipient.
 13. A method oftreating disorders mediated by kallikrein-7 activity, which treatmentcomprises administering to a subject in need of such treatment aneffective amount of a compound of claim
 7. 14-15. (canceled)
 16. Themethod of claim 14 wherein said disorder which is mediated bykallikrein-7 activity is selected from the group consisting ofinflammatory and/or hyperpoliferative and pruritic skin diseases such askeloids, hypertrophic scars, acne, atopic dermatitis, psoriasis,pustular psoriasis, rosacea, Netherton's syndrome or other pruriticdermatoses such as prurigo nodularis, unspecified itch of the elderly aswell as other diseases with epithelial barrier dysfunction such as agedskin, inflammatory bowel disease and Crohn's disease, as well aspancreatitis, or of cancer, in particular ovarian cancer.